Mayo Medical Manual PDF

Mayo Clinic
Medical Manual
This page intentionally left blank
Mayo Clinic
Medical Manual
Editors
Guilherme H. M. Oliveira, M.D.

Gillian C. Nesbitt, M.D.
Joseph G. Murphy, M.D.
MAYO CLINIC SCIENTIFIC PRESS

TAYLOR & FRANCIS GROUP
ISBN 0849390877
The triple-shield Mayo logo and the words MAYO, MAYO CLINIC,
and MAYO CLINIC SCIENTIFIC PRESS are marks of Mayo
Foundation for Medical Education and Research.
2006 by Mayo Foundation for Medical Education and Research.
All rights reserved. This book is protected by copyright. No part of it
may be reproduced, stored in a retrieval system, or transmitted, in any
form or by any meanselectronic, mechanical, photocopying, recording, or otherwisewithout the prior written consent of the copyright
holder, except for brief quotations embodied in critical articles and
reviews. Inquiries should be addressed to Scientific Publications,
Plummer 10, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
For order inquiries, contact Taylor & Francis Group, 6000 Broken
Sound Parkway NW, Suite #300, Boca Raton, FL 33487.
www.taylorandfrancis.com
Catalog record is available from the Library of Congress.
Care has been taken to confirm the accuracy of the information presented
and to describe generally accepted practices. However, the authors,
editors, and publisher are not responsible for errors or omissions or
for any consequences from application of the information in this book
and make no warranty, express or implied, with respect to the contents
of the publication. This book should not be relied on apart from the
advice of a qualified health care provider.
The authors, editors, and publisher have exerted efforts to ensure
that drug selection and dosage set forth in this text are in accordance
with current recommendations and practice at the time of publication.
However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy
and drug reactions, the reader is urged to check the package insert for
each drug for any change in indications and dosage and for added
warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have
Food and Drug Administration (FDA) clearance for limited use in
restricted research settings. It is the responsibility of the health care
providers to ascertain the FDA status of each drug or device planned
for use in their clinical practice.
PREFACE
The urge to write this bookand it was indeed an urgearose
because of two reasons. The first was the lack of a book that
approached patient care from the viewpoint of on-call medical
residents. New residents faced with admitting a sick patient in
the middle of the night have three priorities: one, a working
diagnosis; two, a management plan that will get the patient
through the night; and three, deciding when to call for help
from the attending physician. This on-call manual seeks to
empower residents to reach a working diagnosis and to develop
a short-term management plan using the clinical history, physical
examination, and essential on-call investigations. The layout
of the book allows the reader to look up signs, symptoms, and
laboratory abnormalities; to develop a list of differential diagnoses; and to formulate a management plant. Residents were
recruited to write all the chapters in conjunction with the attending staff.
In conclusion, this Manual intends to be a uniquely useful tool
for young doctors. We hope we have been able to blend the
simplicity and focus essential to the the neophyte with the
knowledge and precision required by the expert.
LIST OF CONTRIBUTORS
Andrea C. Adams, M.D.
Consultant, Department of Neurology, Mayo Clinic; Assistant
Professor of Neurology, Mayo Clinic College of Medicine;
Rochester, Minnesota
Timothy R. Aksamit, M.D.
Consultant, Division of Pulmonary and Critical Care Medicine,
Mayo Clinic; Assistant Professor of Medicine, Mayo Clinic College
of Medicine; Rochester, Minnesota
Robert C. Albright, Jr., D.O.
Consultant, Division of Nephrology and Hypertension, Mayo Clinic;
Assistant Professor of Medicine, Mayo Clinic College of Medicine;
Amindra S. Arora, M.B.B.Chir.
Consultant, Division of Gastroenterology and Hepatology, Mayo
Clinic; Assistant Professor of Medicine, Mayo Clinic College of
Medicine; Rochester, Minnesota
Rendell W. Ashton, M.D.
Fellow in Pulmonary and Critical Care Medicine, Mayo School of
Graduate Medical Education and Instructor in Medicine, Mayo
Clinic College of Medicine, Rochester, Minnesota
Rebecca S. Bahn, M.D.
Consultant, Division of Endocrinology, Diabetes, Metabolism,
Nutrition, Mayo Clinic; Professor of Medicine, Mayo Clinic College
Kiran M. Bambha, M.D.
Fellow in Gastroenterology and Hepatology, Mayo School of
J. D. Bartleson, M.D.
Consultant, Department of Neurology, Mayo Clinic; Associate
T. Jared Bunch, M.D.
Fellow in Cardiovascular Diseases, Mayo School of Graduate
Medical Education and Assistant Professor of Medicine, Mayo
John B. Bundrick, M.D.
Consultant, Division of General Internal Medicine, Mayo Clinic;
vii
Kevin A. Bybee, M.D.

Resident in Cardiovascular Diseases, Mayo School of Graduate
Medical Education and Instructor, Mayo Clinic College of Medicine,
Casey R. Caldwell, M.D.
Consultant, Division of Primary Care Internal Medicine, Mayo
Clinic; Instructor in Medicine, Mayo Clinic College of Medicine;
Sean M. Caples, D.O.
Senior Associate Consultant, Division of Pulmonary and Critical
Care Medicine, Mayo Clinic; Assistant Professor of Medicine,
Mayo Clinic College of Medicine; Rochester, Minnesota
Paul E. Carns, M.D.
Consultant, Department of Anesthesiology, Mayo Clinic; Assistant
Professor of Anesthesiology, Mayo Clinic College of Medicine;
Gregory D. Cascino, M.D.
Consultant, Department of Neurology, Mayo Clinic; Professor of
Neurology, Mayo Clinic College of Medicine; Rochester, Minnesota
Yoon-Hee K. Cha, M.D.
Formerly, Student, Mayo Medical School, Mayo Clinic College
of Medicine, Rochester, Minnesota; presently, Chief Resident in
Neurology, UCSF, San Francisco, California
Suresh T. Chari, M.D.
Clinic; Associate Professor of Medicine, Mayo Clinic College of
Lin Y. Chen, M.D.
Resident in Internal Medicine, Mayo Graduate School of Medicine;
Instructor in Medicine, Mayo Clinic College of Medicine; Rochester,
Minnesota
Lisa S. Chow, M.D.
Fellow in Endocrinology, Diabetes, Metabolism, Nutrition, Mayo
School of Graduate Medical Education and Instructor in Medicine,
Mayo Clinic College of Medicine, Rochester, Minnesota
David Allan Cook, M.D.
Resident in Gastroenterology and Hepatology, Mayo School of
Graduate Medical Education, Mayo Clinic College of Medicine,
Douglas J. Creedon, M.D.
Senior Associate Consultant, Division of Obstetrics, Mayo Clinic,
Arjun Deb, M.D.
Medical Education, Mayo Clinic College of Medicine, Rochester,
Minnesota
viii
Ives R. De Chazal, M.D.

Fellow in Critical Care Medicine, Mayo School of Graduate Medical
Education, Mayo Clinic College of Medicine, Rochester, Minnesota
Ramona S. deJesus, M.D.
Senior Associate Consultant, Division of Primary Care Internal
Medicine, Mayo Clinic; Instructor in Medicine, Mayo Clinic College
Shamina Dhillon, M.D.
Lisa A. Drage, M.D.
Consultant, Department of Dermatology, Mayo Clinic; Assistant
Professor of Dermatology, Mayo Clinic College of Medicine;
William F. Dunn, M.D.
Mayo Clinic; Associate Professor of Medicine, Mayo Clinic College
Grace K. Dy, M.D.
Jon O. Ebbert, M.D., M.Sc.
Randall S. Edson, M.D.
Consultant, Division of Infectious Diseases, Mayo Clinic; Professor
of Medicine, Mayo Clinic College of Medicine; Rochester,
Minnesota
Scott D. Eggers, M.D.
Senior Associate Consultant, Department of Neurology, Mayo
Clinic; Assistant Professor of Neurology, Mayo Clinic College of
Lynn L. Estes, Pharm.D.
Infectious Disease Pharmacist Specialist, Mayo Clinic; Assistant
Professor of Pharmacy, Mayo Clinic College of Medicine;
Luke T. Evans, M.D.
Fernando C. Fervenza, M.D.
Consultant, Division of Nephrology, Mayo Clinic; Associate Professor
of Medicine, Mayo Clinic College of Medicine; Rochester, Minnesota
ix
Javier D. Finkielman, M.D.

Fellow in Nephrology and Hypertension, Mayo School of Graduate
Medical Education and Instructor in Medicine, Mayo Clinic College
of Medicine, Rochester, Minnesota
Matthew L. Flaherty, M.D.
Resident in Neurology, Mayo School of Graduate Medical
Rafael Fonseca, M.D.
Consultant, Division of Hematology, Mayo Clinic; Associate
Professor of Medicine, Mayo Clinic College of Medicine; Rochester,
Minnesota
David A. Froehling, M.D.
Apoor S. Gami, M.D.
Medical Education and Assistant Professor of Medicine, Mayo
Gunjan Y. Gandhi, M.D.
Fellow in Endocrinology, Diabetes, Metabolism, Nutrition and Instructor
in Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
Dennis A. Gastineau, M.D.
Consultant, Division of Hematology, Mayo Clinic; Associate
Minnesota
Anna M. Georgiopoulos, M.D.
Chief Resident Associate in Primary Care Internal Medicine, Mayo
School of Graduate Medical Education, Mayo Clinic College of
Medicine, Rochester, Minnesota
Karin F. Giordano, M.D.
Fellow in Hematology, Mayo School of Graduate Medical
John W. Graves, M.D.
Consultant, Division of Nephrology and Hypertension, Mayo Clinic;
Associate Professor of Medicine, Mayo Clinic College of Medicine;
Stephen F. Grinton, M.D.
Consultant, Division of Pulmonary Medicine, Mayo Clinic,
Jacksonville, Florida; Associate Professor of Medicine, Mayo Clinic
College of Medicine, Rochester, Minnesota
Geeta G. Gyamlani, M.D.
Thomas M. Habermann, M.D.

Consultant, Division of Hematology, Mayo Clinic; Professor of
Medicine, Mayo Clinic College of Medicine; Rochester, Minnesota
J. Eileen Hay, M.B.Ch.B.
Clinic; Professor of Medicine, Mayo Clinic College of Medicine;
John A. Heit, M.D.
Consultant, Division of Cardiovascular Diseases, Mayo Clinic;
Minnesota
Robert W. Hoel, Pharm.D.
Pharmacist, Hospital Pharmacy Services, Mayo Clinic, Rochester,
Minnesota
Jonathan M. Holmes, B.M., B.Ch.
Chair, Department of Ophthalmology, Mayo Clinic; Professor of
Ophthalmology, Mayo Clinic College of Medicine; Rochester,
Minnesota
Arshad Jahangir, M.D.
Constance Jennings, M.D.
Garvan C. Kane, M.D.
A. Scott Keller, M.D.
Senior Associate Consultant, Division of General Internal Medicine,
Mayo Clinic; Instructor in Medicine, Mayo Clinic College of
Kurt A. Kennel, M.D.
Senior Associate Consultant, Division of Endocrinology, Diabetes,
Metabolism, Nutrition, Mayo Clinic; Assistant Professor of
Medicine, Mayo Clinic College of Medicine; Rochester, Minnesota
Peter D. Kent, M.D.
Fellow in Rheumatology, Mayo School of Graduate Medical
Stephen L. Kopecky, M.D.
xi
Stephen M. Lange, M.D.

Clinic, Jacksonville, Florida; Assistant Professor of Medicine,
Augustine S. Lee, M.D.
Senior Associate Consultant, Division of Pulmonary Medicine,
Mayo Clinic, Jacksonville, Florida; Assistant Professor of Medicine,
Kaiser G. Lim, M.D.
Lionel S. Lim, M.D.
Fellow in Primary Care Internal Medicine, Mayo School of Graduate
Minnesota
Adam J. Locketz, M.D.
Fellow in Pain Medicine, Mayo School of Graduate Medical
Conor G. Loftus, M.D.
Senior Associate Consultant, Division of Gastroenterology and
Hepatology, Mayo Clinic; Assistant Professor of Medicine, Mayo
Clinic College of Medicine; Rochester, Minnesota
Edward V. Loftus, Jr., M.D.
Clinic; Associate Professor of Medicine, Mayo Clinic College of
William F. Marshall, M.D.
Consultant, Division of Infectious Diseases, Mayo Clinic; Assistant
Minnesota
Stanley I. Martin, M.D.
Resident in Endocrinology, Diabetes, Metabolism, Nutrition, Mayo
Matthew W. Martinez, M.D.
Thomas G. Mason, M.D.
Consultant, Division of Rheumatology, Mayo Clinic; Assistant
Professor of Medicine and of Pediatrics, Mayo Clinic College of
Kathleen M. McEvoy, M.D.
xii

Lawrence K. McKnight, M.D.
Resident in Nephrology and Hypertension, Mayo School of
M. Molly McMahon, M.D.
Victor M. Montori, M.D.
Senior Associate Consultant, Division of Endocrinology, Diabetes,
Metabolism, Nutrition, Mayo Clinic, Rochester, Minnesota
Paul S. Mueller, M.D.
William C. Mundell, M.D.
Consultant, Division of General Internal Medicine, Mayo Clinic; Instructor
in Medicine, Mayo Clinic College of Medicine; Rochester, Minnesota
Gillian C. Nesbitt, M.D.
Resident in Internal Medicine, Mayo Clinic College of Medicine,
Senior Resident Associate in Internal Medicine, Mayo School of
Amy S. Oxentenko, M.D.
Graduate Medical Education and Assistant Professor of Medicine,
Darrell S. Pardi, M.D.
Miguel A. Park, M.D.
Senior Associate Consultant, Division of Allergic Diseases, Mayo
Clinic; Instructor in Medicine, Mayo Clinic College of Medicine;
Sanjay V. Patel, B.M., B.Ch.
Senior Associate Consultant, Department of Ophthalmology, Mayo
xiii
Clinic; Assistant Professor of Ophthalmology, Mayo Clinic College

Jason Persoff, M.D.
Senior Associate Consultant, Division of Hospital Internal Medicine,
Mayo Clinic, Jacksonville, Florida; Assistant Professor of Medicine,
Steve G. Peters, M.D.
Mayo Clinic; Professor of Medicine, Mayo Clinic College of
David H. Pfizenmaier II, M.D., D.P.M.
Senior Resident in Cardiovascular Diseases, Mayo School of
Axel Pflueger, M.D.
Fellow in Infectious Diseases, Mayo School of Graduate Medical
Education and Instructor in Medicine, Mayo Clinic College of
Udaya B. S. Prakash, M.D.
Rajiv K. Pruthi, M.B.B.S.
Consultant, Division of Hematology, Mayo Clinic; Assistant Professor
of Medicine, Mayo Clinic College of Medicine; Rochester, Minnesota
Jeffrey T. Rabatin, M.D.
Otis B. Rickman, D.O.
Douglas L. Riegert-Johnson, M.D.
Resident in Pulmonary and Critical Care Medicine, Mayo School
of Graduate Medical Education, Mayo Clinic College of Medicine,
Vanessa Z. Riegert-Johnson
Student, Mayo Medical School, Mayo Clinic College of Medicine,
Charanjit S. Rihal, M.D.
Minnesota
Thom W. Rooke, M.D.
xiv

Minnesota
Edward C. Rosenow III, M.D.
Emeritus Consultant, Division of Pulmonary and Critical Care
Medicine, Mayo Clinic; Emeritus Professor of Medicine, Mayo
Clinic College of Medicine; Rochester, Minnesota
Andrew D. Rule, M.D.
Fellow in Nephrology and Hypertension, Mayo School of Graduate
William Sanchez, M.D.
Graduate Medical Education and Instructor of Medicine, Mayo
Paul D. Scanlon, M.D.
Nicola E. Schiebel, M.D.
Consultant, Department of Emergency Medicine, Mayo Clinic;
Assistant Professor of Emergency Medicine, Mayo Clinic College
Alexander Schirger, M.D.
Minnesota
James B. Seward, M.D.
Minnesota
Tait D. Shanafelt, M.D.
Senior Associate Consultant, Division of Hematology, Mayo Clinic;
Clarence Shub, M.D.
Professor of Medicine, Mayo Clinic Collge of Medicine; Rochester,
Minnesota
Marina G. Silveira, M.D.
Ripudamanjit Singh, M.D.
Senior Associate Consultant, Division of Cardiovascular Diseases,
Mayo School of Graduate Medical Education and Assistant Professor
of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
xv
Kirby D. Slifer, D.O.

Resident in Pulmonary and Critical Care Medicine, Mayo School
Jay Smith, M.D.
Consultant, Department of Physical Medicine and Rehabilitation,
Mayo Clinic; Associate Professor of Physical Medicine and
Rehabilitation, Mayo Clinic College of Medicine; Rochester,
Minnesota
Cacia V. Soares-Welch, M.D.
Resident in General Internal Medicine, Mayo School of Graduate
Minnesota
Thomas C. Sodeman, M.D.
Advanced Fellow in Gastroenterology and Hepatology, Mayo
Paul Y. Takahashi, M.D.
Dariush S. Takhtehchian, M.D.
Minnesota
Pierre Theuma, M.D.
Resident in Endocrinology, Diabetes, Metabolism, Nutrition, Mayo
Rochelle R. Torgerson, M.D., Ph.D.
Fellow in Dermatology, Mayo School of Graduate Medical
Santhi Swaroop Vege, M.D.
Minnesota
K. L. Venkatachalam, M.D.
Minnesota
Thomas R. Viggiano, M.D.
Clinic; Professor of Medicine, Mayo Clinic College of Medicine;
Stacey A. R. Vlahakis, M.D.
Senior Associate Consultant, Division of Infectious Diseases, Mayo
xvi

Kenneth J. Warrington, M.D.
Fellow in Rheumatology, Mayo School of Graduate Medical
Edwin G. Wells III, M.D.
Formerly, Student, Mayo Medical School, Mayo Clinic College
of Medicine, Rochester, Minnesota; presently, Resident Physician
in Emergency Medicine, Loma Linda, California
John W. Wilson, M.D.
Minnesota
Walter R. Wilson, M.D.
Professor of Microbiology and Professor of Medicine, Mayo Clinic
College of Medicine; Rochester, Minnesota
Nina Wokhlu, M.D.
Senior Resident Associate in Cardiovascular Diseases, Mayo School
Thomas P. Worley, M.D.
Resident in Hematology, Mayo School of Graduate Medical
Gregory A. Worrell, M.D.
R. Scott Wright, M.D.
William F. Young, Jr., M.D.
Steven J. Younger, M.D.
Resident in Nephrology and Hypertension, Mayo School of
Steven R. Ytterberg, M.D.
Consultant, Division of Rheumatology, Mayo Clinic; Associate
Minnesota
xvii
TABLE OF CONTENTS
Signs and Symptoms
Abdominal Pain Shamina Dhillon, M.D.;
Thomas R. Viggiano, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1
Anemia Miguel A. Park, M.D.; Paul S. Mueller, M.D. . . . . . . . . .11
Back Pain A. Scott Keller, M.D.; Jay Smith, M.D. . . . . . . . . . . . .25
Bleeding Disorders Thomas P. Worley, M.D.;
John A. Heit, M.D.; Rajiv K. Pruthi, M.B.B.S. . . . . . . . . . . . . . . .41
Chest Pain Guilherme H. M. Oliveira, M.D.;
Joseph G. Murphy, M.D.; R. Scott Wright, M.D. . . . . . . . . . . . . .55
Cough, Hemoptysis, and Hiccup Douglas L. RiegertJohnson, M.D.; Vanessa Z. Riegert-Johnson;
Constance Jennings, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .63
Delirium and Dementia Lionel S. Lim, M.D.;
Paul Y. Takahashi, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .73
Diarrhea David Allan Cook, M.D.; Darrell S.
Pardi, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .91
Dizziness and Vertigo Yoon-Hee K. Cha, M.D.; Scott D.
Eggers, M.D.; David A. Froehling, M.D. . . . . . . . . . . . . . . . . . .103
Dyspnea Lin Y. Chen, M.D.; Guilherme H. M. Oliveira,
M.D.; Joseph G. Murphy. M.D. . . . . . . . . . . . . . . . . . . . . . . . . . .109
Electrolyte Disturbances Lawrence K. McKnight,
M.D.; Robert C. Albright, Jr., D.O. . . . . . . . . . . . . . . . . . . . . . . .117
Fever of Unknown Origin Ramona S. deJesus, M.D.;
Randall S. Edson, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .131
Gastrointestinal Tract Bleeding Marina G. Silveira,
M.D.; Amindra S. Arora, M.B.B.Chir. . . . . . . . . . . . . . . . . . . . . .139
Headache Douglas J. Creedon, M.D.; Anna M.
Georgiopoulos, M.D.; J. D. Bartleson, M.D. . . . . . . . . . . . . . . .149
Hematuria Amy S. Oxentenko, M.D.; Fernando C.
Fervenza, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .157
Hemoptysis Otis B. Rickman, D.O.; Udaya B. S.
Prakash, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .171
Hepatomegaly T. Jared Bunch, M.D.; Santhi
Swaroop Vege, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .179
Joint Pain Peter D. Kent, M.D.; Thomas G.
Mason, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .189
Lower Extremity Pain David H. Pfizenmaier II,
M.D., D.P.M.; Thom W. Rooke, M.D. . . . . . . . . . . . . . . . . . . . . .199
Nausea and Vomiting Luke T. Evans, M.D.;
Darrell S. Pardi, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .211
xix
Ocular and Visual Abnormalities Sanjay V. Patel, B.M.,

B.S.; Jonathan M. Holmes, B.M., B.Ch. . . . . . . . . . . . . . . . . . . .219
Palpitations Kevin A. Bybee, M.D.; Stephen L.
Kopecky, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .233
Rash Rochelle R. Torgerson, M.D., Ph.D.; Lisa
A. Drage, M.D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .239
Splenomegaly T. Jared Bunch, M.D.; Thomas M.
Habermann, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .249
Thrombocytopenia Tait D. Shanafelt, M.D.;
Rafael Fonseca, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .259
Tremor and Movement Disorders Matthew L.
Flaherty, M.D.; Andrea C. Adams, M.D. . . . . . . . . . . . . . . . . . . .271
Laboratory Diagnosis
Arterial Blood Gases Grace K. Dy, M.D.;
Kaiser G. Lim, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .281
Cardiac Biomarkers R. Scott Wright, M.D.; Dariush S.
Takhtehchian, M.D.; Joseph G. Murphy, M.D. . . . . . . . . . . . . . .287
Chest X-Ray Sean M. Caples, D.O.; Edward C.
Rosenow III, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .291
Coagulation Panel Karin F. Giordano, M.D.; Rajiv
K. Pruthi, M.B.B.S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .307
Hepatitis Serology William Sanchez, M.D.; J. Eileen
Hay, M.B.Ch.B. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .323
Interpretation of the Electrocardiogram Nina
Wokhlu, M.D.; Clarence Shub, M.D. . . . . . . . . . . . . . . . . . . . . . .327
Liver Function Tests Augustine S. Lee, M.D.;
Jason Persoff, M.D.; Stephen M. Lange, M.D. . . . . . . . . . . . . . .373
Pulmonary Artery Catheter Kirby D. Slifer, D.O.;
William F. Dunn, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .389
Pulmonary Function Tests David Allan Cook, M.D.;
Paul D. Scanlon, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .403
Thyroid Function Tests Lisa S. Chow, M.D.;
Rebecca S. Bahn, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .411
Diseases
Acid-Base Disorders Javier D. Finkielman, M.D.;
Robert C. Albright, Jr., D.O. . . . . . . . . . . . . . . . . . . . . . . . . . . . .417
Acute Coronary Syndromes Guilherme H. M. Oliveira,
M.D.; Arjun Deb, M.D.; R. Scott Wright, M.D.;
Joseph G. Murphy, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .431
Acute Renal Failure Andrew D. Rule, M.D.;
Robert C. Albright, Jr., D.O. . . . . . . . . . . . . . . . . . . . . . . . . . . . .451
xx
Asthma Augustine S. Lee, M.D.; Jason Persoff,

M.D.; Stephen F. Grinton, M.D. . . . . . . . . . . . . . . . . . . . . . . . . .461
Atrial Fibrillation Garvan C. Kane, M.D.;
Arshad Jahangir, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .475
Chronic Obstructive Pulmonary Disease Rendell W.
Ashton, M.D.; Paul D. Scanlon, M.D. . . . . . . . . . . . . . . . . . . . . .485
Congestive Heart Failure Guilherme H. M. Oliveira,
M.D.; Joseph G. Murphy, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . .497
Connective Tissue Diseases Kenneth J. Warrington,
M.D.; Steven R. Ytterberg, M.D. . . . . . . . . . . . . . . . . . . . . . . . . .509
Diabetes Mellitus Gunjan Y. Gandhi, M.D.; Pierre
Theuma, M.D.; Victor M. Montori, M.D. . . . . . . . . . . . . . . . . . .529
Epileptic Seizures Yoon-Hee K. Cha; Gregory A.
Worrell, M.D.; Gregory D. Cascino, M.D. . . . . . . . . . . . . . . . . .539
Fulminant Hepatic Failure Thomas C. Sodeman,
M.D.; J. Eilene Hay, M.B.Ch.B. . . . . . . . . . . . . . . . . . . . . . . . . .551
HIV Disease Complications Kiran M. Bambha, M.D.;
Stacey A. R. Vlahakis, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .555
Hypertensive Crisis Guilherme H. M. Oliveira,
M.D.; Alexander Schirger, M.D. . . . . . . . . . . . . . . . . . . . . . . . . .609
Infective Endocarditis Axel Pflueger, M.D.;
Walter R. Wilson, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .615
Inflammatory Bowel Disease Conor G. Loftus,
M.D.; Edward V. Loftus, Jr., M.D. . . . . . . . . . . . . . . . . . . . . . . . .641
Myasthenia Gravis and Disorders of the Neuromuscular
Junction Guilherme H. M. Oliveira, M.D.;
Kathleen M. McEvoy, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .653
Neutropenia Tait D. Shanafelt, M.D.; Rafael
Fonseca, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .661
Pancreatitis Marina G. Silveira, M.D.; Suresh
T. Chari, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .667
Pericardial Diseases Guilherme H. M. Oliveira,
M.D.; James B. Seward, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . .687
Pneumonia David Allan Cook, M.D.; Randall S.
Edson, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .697
Poisonings and Overdoses Geeta G. Gyamlani, M.D.;
William F. Dunn, M.D.; Robert W. Hoel, Pharm. D. . . . . . . . . . .705
Pulmonary Thromboembolism Ives R. De Chazal,
M.D.; William F. Dunn, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . .719
Sepsis Axel Pflueger, M.D.; Timothy R. Aksamit, M.D. . . . . . . . .727
Urinary Tract Infections Kirby D. Slifer, D.O.;
William F. Marshall, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .741
Vasculitis Peter D. Kent, M.D.; Thomas G.
Mason, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .749
xxi
Therapy
Antimicrobial Agents John W. Wilson M.D.;
Lynn L. Estes, Pharm.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .763
Cardiac Arrest Joseph G. Murphy, M.D.; Gillian C.
Nesbitt, M.D.; R. Scott Wright, M.D. . . . . . . . . . . . . . . . . . . . . . .809
Insulin Therapy for Hospitalized Patients Cacia V.
Soares-Welch, M.D.; William C. Mundell, M.D. . . . . . . . . . . . . .813
Lipid Management R. Scott Wright, M.D.; Gillian C.
Nesbitt, M.D.; Joseph G. Murphy, M.D. . . . . . . . . . . . . . . . . . . .821
Mechanical and Noninvasive Positive Pressure
Ventilation Kirby D. Slifer, D.O. ; Steve G.
Peters, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .825
Nutrition Support in Hospitalized Patients Kurt A.
Kennel, M.D.; M. Molly McMahon, M.D. . . . . . . . . . . . . . . . . . .841
Oxygen Therapy Apoor S. Gami, M.D.; Jeffrey
T. Rabatin, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .853
Pain Management K. L. Venkatachalam, M.D.;
Paul E. Carns, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .861
Procedures Matthew W. Martinez, M.D.; Adam J.
Locketz, M.D.; Jon O. Ebbert, M.D., M.Sc. . . . . . . . . . . . . . . . .875
Renal Replacement Therapies Steven J. Younger,
M.D.; John W. Graves, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . .895
Steroid Therapy Stanley I. Martin, M.D.; William
F. Young, Jr., M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .901
Transfusion Therapy Grace K. Dy, M.D.; Dennis
A. Gastineau, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .911
Insights
Emergency Response Team Responsibilities and
Guidelines Rendell W. Ashton, M.D.; T. Jared
Bunch, M.D.; Edwin G. Wells III, M.D.; Nicola
E. Schiebel, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .925
End of Life Anna M. Georgiopoulos, M.D.;
Casey R. Caldwell, M.D. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .939
Eponyms in Internal Medicine Guilherme H. M.
Oliveira, M.D.; John B. Bundrick, M.D. . . . . . . . . . . . . . . . . . . .955
Evidence-Based Practice Guilherme H. M. Oliveira,
M.D.; Victor M. Montori, M.D., M.Sc. . . . . . . . . . . . . . . . . . . . .983
How to Be a Good Intern Jason Persoff, M.D. . . . . . . . . . . . . .989
Preoperative Medical Evaluation Ripudamanjit
Singh, M.D.; Charanjit S. Rihal, M.D. . . . . . . . . . . . . . . . . . . .1015
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1033
xxii
ABBREVIATIONS
The following abbreviations are used in the text, tables, and figure
legends and are defined only here:
AIDS
ALT
aPTT
AST
BUN
CBC
CK
CK-MB
COPD
CSF
CT
ECG
EEG
EMG
ESR
HIV
ICU
IM
INR
IV
LDH
MRI
NPO
NSAID
PMN
PO
PT
PTT
RBC
SQ
TB
WBC
acquired immunodeficiency syndrome

alanine aminotransferase
activated partial thromboplastin time
aspartate aminotransferase
blood urea nitrogen
complete blood count
creatine kinase
creatine kinase, muscle & brain subunits
chronic obstructive pulmonary disease
cerebrospinal fluid
computed tomography
electrocardiography
electroencephalography
electromyography
erythrocyte sedimentation rate
human immunodeficiency virus
intensive care unit
intramuscular
international normalized ratio
intravenous
lactate dehydrogenase
magnetic resonance imaging
nothing by mouth
nonsteroidal antiinflammatory drug
polymorphonuclear neutrophil
by mouth, orally
prothrombin time
partial thromboplastin time
red blood cell
subcutaneous
tuberculosis
white blood cell
Other, less frequent abbreviations are defined when first used in each
chapter.
xxiii
I SIGNS & SYMPTOMS

ABDOMINAL PAIN
Shamina Dhillon, M.D.
Thomas R. Viggiano, M.D.
IS THE PATIENTS LIFE AT RISK?

Abdominal pain is a common sign encountered by interns.
Vital signs and general appearance are clues to urgency of the
underlying problem.
Pain in conjunction with the abnormalities below often points
to certain conditions that indicate imminent danger.
Hypotension and/or Tachycardia
Bleedingperforated viscus, ruptured aortic aneurysm,
aortic dissection, ruptured spleen or solid organ (kidney,
liver)
Inflammatory response syndrome or sepsisnecrotizing
fasciitis, secondary peritonitis, spontaneous bacterial peritonitis, acute pancreatitis
Volume depletionbowel obstruction, acute pancreatitis
Tissue hypoperfusionacute myocardial infarction, severe
heart failure, mesenteric infarction
Altered Mental Status

Cerebral hypoperfusionaortic hypoperfusion, ruptured
aortic aneurysm, myocardial infarction, advanced sepsis
Severe metabolic derangementspontaneous bacterial peritonitis, advanced sepsis, necrotizing panniculitis, mesenteric
infarction
Hypoxemiapulmonary embolism, myocardial infarction,
sepsis
Tachypnea and Low Oxygen Saturation

Pulmonary embolism
Heart failure
Myocardial infarction
In addition to the above, certain clinical observations and physical examination findings point to specific life-threatening diagnoses in patients with abdominal pain. The presence of these
findings should alert interns to a potentially harmful situation
for the patient.
Worrisome Physical Findings
Abdominal rigidityperforated viscus
Hypoactive or absent bowel soundsperforated viscus,
bowel obstruction, ischemic gut
Patients position
Lying stillperforated viscus, myocardial infarction
Restless/writhingbowel obstruction, ischemic bowel
Character of Pain
Burningperforated ulcer and myocardial infarction
Dullacute appendicitis and myocardial infarction
Tearingaortic dissection
Constrictingacute cholecystitis, myocardial infarction
Boringacute pancreatitis, expanding abdominal aortic
aneurysm
Crampybowel obstruction
Diffuseruptured abdominal aortic aneurysm, bowel
obstruction, peritonitis, heart failure
Onset of Pain
Suddenperforated ulcer, ruptured abdominal aortic
aneurysm, aortic dissection, ruptured ectopic pregnancy,
bowel ischemia
Rapidacute pancreatitis, acute cholecystitis
Gradualacute appendicitis, bowel obstruction
Radiation of Pain
Back/flankabdominal aortic dissection, pancreatitis
Scapulaacute cholecystitis
Right lower quadrantacute appendicitis
ADDRESSING THE RISK

Serial abdominal exams are essential when managing patients
with abdominal pain. The following measures are indicated
I SIGNS & SYMPTOMS

for monitoring patients with abdominal pain and the
associated condition listed below.
Hypotension
Check orthostatic blood pressure as the patient tolerates.
Establish large-bore IV access.
Place Foley catheter to monitor urine output and adjust fluids.
If blood pressure is not responding to fluid challenge, transfer to ICU for monitoring and initiate pressors.
Involve surgery early if vascular catastrophe is suspected.
Type and crossmatch 2-4 RBC units.
ECG
Tachycardia
Large-bore IV access
Normal saline IV initially to increase intravascular volume
maximally
Consider type and crossmatch early.
Oliguria
Foley catheter for accurate urine output
Remember: urine is liquid gold, keep it flowing.
Fluid challenge to meet urine output goal of 0.5 mL/kg per hour
Altered Mental Status

Check arterial blood gas values early.
Replace volume to ensure adequate blood pressure and perfusion to vital organs.
Check electrolyte panel early because certain imbalances
such as hypercalcemia can mimic abdominal pain and altered
mental status.
Check ECG and chest X-ray to rule out potential sources of
hypoxia or hypercarbia.
DIFFERENTIAL DIAGNOSIS
The differential diagnosis by anatomical location is listed
in Table 1 and the extra-abdominal causes of pain are listed
in Table 2.
Table 1. Differential Diagnosis by Anatomical Location

Left upper quadrant
Empyema
Gastritis
Pancreatitis
Pneumonia
Pulmonary infarction
Splenic artery aneurysm
Splenic infarct
Splenomegaly
Left lower quadrant
Colon cancer
Diverticulitis
Ectopic pregnancy
Endometriosis
Intestinal obstruction
Ovarian cyst
Pelvic inflammatory disease
Renal calculi
Ulcerative colitis
Diffuse abdominal pain
Abdominal aortic aneurysm
Appendicitis
Colitis
Gastroenteritis
Inflammatory bowel disease
Intestinal ischemia
Mesenteric venous thrombosis
Spontaneous bacterial peritonitis
Right upper quadrant

Cholangitis
Cholecystitis
Choledochal cyst
Choledocholithiasis
Hepatic abscess
Hepatic metastasis
Hepatitis
Hepatomegaly
Pancreatitis
Peptic ulcer
Pneumonia
Subphrenic abscess
Right lower quadrant
Appendicitis
Crohn disease
Diverticulitis
Ectopic pregnancy
Endometriosis
Gastroenteritis
Meckel diverticulitis
Mesenteric lymphadenitis
Ovarian cyst
Renal calculi
Ruptured peptic ulcer
Salpingitis
Ulcerative colitis
Epigastrium
Cholecystitis
Myocardial ischemia
Pancreatitis
Peptic ulcer
Reflux esophagitis
I SIGNS & SYMPTOMS

Table 2. Extra-abdominal Causes of Pain
Cardiac
Myocardial ischemia or
infarction
Congestive heart failure
Endocarditis
Myocarditis
Thoracic
Pneumonitis
Pleurodynia
Pulmonary embolism
Pneumothorax
Empyema
Esophagitis
Esophageal spasm
Esophageal rupture
Neurologic
Radiculitisspinal cord or
peripheral
Nerve tumors
Arthritis of spine
Abdominal epilepsy
Tabes dorsalis
Metabolic
Uremia
Diabetes mellitus
Porphyria
Acute adrenal insufficiency
Hyperlipidemia
Hyperparathyroidism
(hypercalcemia)
Hematologic
Sickle cell anemia
Hemolytic anemia
Acute leukemia
Henoch-Schnlein purpura
Toxic
Hypersensitivity reaction
insect bites, reptile venoms
Lead poisoning
Infectious
Herpes zoster
Osteomyelitis
Typhoid fever
Miscellaneous
Muscular contusion, hematoma, or tumor
Narcotic withdrawal
Familial Mediterranean fever
Psychiatric disorders
DIFFERENTIATING THE DIFFERENTIAL

After first managing any immediate threat to a patient with
abdominal pain, the history and physical exam can lead to the
diagnosis.
The history and physical findings that should be ascertained
when considering various causes of abdominal pain are listed in Table 3.
The history and physical findings that may be helpful in localizing the problem to a specific organ are listed in Table 4.
5
Table 3. Differentiating by Etiology

Vascular
History
Postprandial pain
Coronary artery disease
Atherosclerosis
Claudication
Physical
Atrial fibrillation
Cardiac arrhythmia
Pulsatile mass
Diminished peripheral
pulses
Abdominal bruits
Pain out of proportion
to physical findings
Infectious
History
NVD before pain
Detailed food history
Travel history
Fever
Physical
Bloody diarrhea
Diffuse tenderness
Mechanical obstruction
History
Previous surgical procedures
Weight loss from malignancy
Fever from lymphoma
Change in bowel habits
Bilious emesis
Physical
Abdominal scars
Abdominal wall mass
Abdominal distension
Hypoactive bowel sounds
Inguinal hernia
Metabolic
History
Polyuria
Polydipsia
Change in urine
output
Fatigue
Lead exposure
Physical
Dry mucous membranes
Hypotension
NVD, nausea, vomiting, diarrhea; STD, sexually transmitted disease; TAH, total abdominal hysterectomy.
Gynecologic causes
History
Date of last menstrual period
Previous cesarean section
or TAH
Dysfunctional uterine bleeding
Alteration in menstrual cycle
STD history
Vaginal discharge
Dysuria
Physical
Cervical motion tenderness
Adnexal tenderness
Vaginal discharge
Table 4. Differentiating by Organ System

Esophagus
History
NSAID use
Relief with
antacid use
Smoking
Alcohol
Physical
Epigastric tenderness
Small intestine
History
Flatus
Last bowel movement
Physical
Abdominal distension
Visible peristaltic
wave
Colon
Biliary tract
History
History of inflammatory bowel
disease
History of diverticulosis
Tenesmus
Physical
Distension
History
Drug/alcohol use
Change in stool/
urine color
History of transfusions
Alcohol use
History of gallstones
Physical
Jaundice
Pancreas
History
Alcohol use
History of gallstones
Steatorrhea
Physical
Epigastric tenderness
Cullen sign
Grey Turner sign
I SIGNS & SYMPTOMS
History
Excessive emesis
(Boerhaave)
Alcohol abuse
Heartburn
Dysphagia
Physical
Subcutaneous
emphysema
Stomach
DIAGNOSTIC TEST ORDERING

For all patients with abdominal pain, the following lab tests
should be ordered:
CBC with differential
Electrolytes
Urinalysis
Pregnancy test in women of childbearing age
CT of abdomen with and without contrast
The appropriate tests for various signs and symptoms are
given in Table 5.
Diagnostic tests for specific disease states are listed in Table 6.
INITIAL MANAGEMENT
Abdominal Aortic Aneurysm Rupture
Surgical emergency!
Type and crossmatch at least 4 units of blood immediately.
Resuscitate with fluids and blood as needed until operating
room is ready.
Preoperative antibiotic prophylaxis
Acute Cholecystitis
Start fluids0.9 normal saline for replacement, initial fluid
bolus if hypovolemic
Table 5. Appropriate Tests According to Signs and

Symptoms
Signs/symptoms
Fever, abdominal pain
Peritoneal signs
RUQ pain
Epigastric pain
Diarrhea, fever
Pulsatile mass
Diffuse pain, atherosclerosis risk
Appropriate tests
CBC, blood cultures, paracentesis if
ascites, CT
Abdominal filmflat and upright, CT
Ultrasound, AST, ALT, alkaline
phosphatase, total/direct bilirubin, CT
Amylase, lipase, AST, ALT, ultrasound,
CT
Fecal WBCs, stool bacterial & parasite
cultures, Clostridium difficile toxin if
recent antibiotic use
Abdominal ultrasound, CT
LDH, ABG to assess acidosis, ECG,
angiography with contrast CT
ABG, arterial blood gases; RUQ, right upper quadrant.

8
I SIGNS & SYMPTOMS

Table 6. Diagnostic Tests for Specific Disease States
Suspected diagnosis
Ruptured abdominal
aortic aneurysm,
aortic dissection
Perforated viscus
Bowel obstruction
Acute pancreatitis
Appendicitis
Cholecystitis
Ruptured ectopic
pregnancy
Diagnostic modalities
CT
Ultrasound
Plain upright film (pneumoperitoneum
in 75% of patients)
CT with water-soluble contrast to
localize perforation
Plain abdominal films
CT
Lipase (sensitivity, 60%; specificity,
80%-99%), CT if complications suspected
Ultrasound
Ultrasound (positive predictive value
of Murphy sign, 90%)
Transvaginal ultrasound (sensitivity,
84.4%; specificity, 98.9% if positive
pregnancy test)
NPO except oral medication

Start antibioticspiperacillin-tazobactam (Zosyn)* 3.375
mg IV every 6 hours if renal function is preserved
Surgical consult
Nasogastric suctioning if persistent emesis
Acute Appendicitis
NPO
Start fluids
Ampicillin-sulbactam (Unasyn)* 3 g IV every 6 hours
Surgical consult
Antipyretics
Acute Pancreatitis
NPO
Nasogastric tube if emesis
*These antibiotics are suggestions and can be modified as indicated
by the clinical scenario.

9
Aggressive fluid therapy because fluid depletion is usually

between 1 and 3 L
Foley catheter to monitor urine output, at least 0.5 mL/kg
per hour
Oxygen
Alcohol withdrawal prophylaxis
H2-blockers
Imipenem if necrosis is suspected
Monitor calcium and magnesium levels.
Analgesia for pain control
Think ahead for nutritional support if long-term NPO status.
Small-Bowel Obstruction
NPO
H -blockers
2
Nasogastric tube
Fluid therapy
Serial abdominal exams every 6 hours
Piperacillin-tazobactam* 3.375 mg IV every 6 hours if renal
function preserved
Acute Diverticulitis
Metronidazole (Flagyl)* 500 mg 4 times daily and levofloxacin (Levaquin)* 500 mg PO once daily
Bowel rest
NPO
IV fluids
*These antibiotics are suggestions and can be modified as indicated
by the clinical scenario.

10
I SIGNS & SYMPTOMS

ANEMIA
Miguel A. Park, M.D.
Paul S. Mueller, M.D.

Several clinical situations involving anemic patients warrant immediate evaluation and treatment.
Active bleeding, especially if hypovolemia or shock is
present
Evidence of myocardial ischemia (e.g., angina pectoris,
myocardial infarction) and/or ischemia of other tissues
Evidence of new-onset hemolysis
ADDRESSING THE RISK
Active Bleeding, Especially if Hypovolemia or Shock Is
Present
Obtain IV access with 2 large-bore (16-gauge if possible)
catheters for rapid fluid resuscitation and/or transfusion.
Resistance to flow is determined by both the length and diameter of the catheter. A short peripheral IV catheter causes less
resistance to flow than a long central line of the same diameter. Hence, peripheral IV catheters may be better suited for
rapid fluid resuscitation and/or transfusion than a central line.
If the clinical situation allows, type and crossmatch the
patients blood. Otherwise, give type O-negative blood.
Closely monitor for evidence of hypovolemia and shock
(e.g., blood pressure, jugular venous pressure, urine output).
Identify and address the source of bleeding.
Evidence of Myocardial Ischemia and/or Ischemia
of Other Tissues
Appropriately evaluate and treat myocardial ischemia.
Special abbreviation used in this chapter: RI, reticulocyte index.
11
If hemoglobulin is <10 g/dL and/or hematocrit is 30%,

some evidence suggests that RBC transfusions may be
beneficial.
Evidence of New-Onset Hemolysis

Assess for myocardial and other tissue ischemia (see above).
Request an immediate hematology consult.
If evidence of thrombotic thrombocytopenic purpura, prepare for possible plasma exchange.
Definition
Anemia is defined by the World Health Organization as
hemoglobin <12 g/dL in women and <13 g/dL in men
A history and physical exam are the first steps in the evaluation
of anemia.
History
Is there a personal and/or family history of anemia (e.g., sickle cell, thalassemia, hereditary spherocytosis)?
Are there any past or present medical conditions that can cause
anemia (e.g., rheumatoid arthritis, systemic lupus erythematosus, chronic renal failure, gastroesophageal reflux disease with Cameron erosions, liver disease, endocrine disease)?
Review for medications that may cause anemia (e.g.,
NSAIDs, anticoagulants, alcohol, chemotherapy agents).
Is there a history of blood loss (e.g., menorrhagia, bloody
or black stools, hematemesis, blood-tinged urine, retroperitoneal hemorrhage)?
What is the patients general nutritional state (e.g., involuntary weight loss)?
Is there a history of a recent viral illness (which is associated with aplastic anemia)?
If female, is the patient of childbearing age (e.g., pregnancy,
HELLP syndrome)? Note: HELLP is hemolytic anemia,
elevated liver function tests, low platelets.
Physical Exam
Skin, nails, and eyes
12
I SIGNS & SYMPTOMS

Jaundice (hemolysis)
Bruising and ecchymoses (e.g., aplastic anemia, myelodysplastic syndrome)
Koilonychia, or spooning of the nails (iron deficiency)
Atrophic glossitis and angular stomatitis (iron deficiency)
Pallor
Lymphadenopathy
Cardiovascular
Malfunctioning mechanical valve (hemolysis)
Murmur
Abdominal/rectal
Hepatosplenomegaly
Rectal exam for blood and mass
Musculoskeletal
Bone tenderness or pain (e.g., leukemia, multiple myeloma, metastatic cancer)
Pelvic examination, especially if child-bearing age (ruptured
ectopic pregnancy)
Neurologic
Loss of vibration and position sense (vitamin B12 deficiency)
Any site of biopsy or surgical wound
Figures 1-3 and Tables 1-9 assist in evaluating patients who
have common causes of anemia.
Table 1. Microcytic AnemiaMean Corpuscular

Volume <80 fL
Iron deficiency (see Table 4)
Thalassemia syndromes
Anemia of chronic disease
Lead poisoning
Sideroblastic anemia
Celiac sprue
Vitamin B6 deficiency
13
Table 2. Macrocytic AnemiaMean Corpuscular

Volume >100 fL
Alcohol abuse
Vitamin B12/folate deficiency
Liver disease
Hypothyroidism
Chemotherapy/drugs (see Table 5)
Myelodysplasia
Reticulocytosis
Cell-counter artifact
Table 3. Normocytic AnemiaMean Corpuscular

Volume 80-100 fL
Decreased production (see Table 6)
Increased destruction (see Table 7)
Early blood loss
Table 4. Iron Deficiency Anemia

Blood loss
Increased
requirement
Gastrointestinal ulcers,
malignancies, sprue,
esophagitis, etc.
Menstruation
Phlebotomy, surgery, trauma
Genitourinary: renal cell
cancer, paroxysmal nocturnal
hemoglobinuria, etc.
Infections: schistosomiasis,
hookworm, etc.
Pregnancy
Decreased
absorption
Partial gastrectomy
Malabsorption
syndromes
Sprue
Table 5. Medications Associated With Macrocytosis

Alcohol
Azathioprine
Cytosine arabinoside (cytarabine)
5-Fluorouracil
Hydroxyurea
Methotrexate
Oral contraceptives
14
Phenobarbital
Phenytoin
Primidone
Sulfamethoxazole
Sulfasalazine
Triamterene
Zidovudine
Table 6. Differential Diagnosis of Decreased Production in Normocytic Anemias

Inflammatory states/
anemia of chronic
disease
End-stage renal
disease
Nephritis
Hypometabolic/hypermetabolic states
Protein deprivation
Endocrine deficiency states
Hypothyroidism
Hypopituitarism
Adrenal insufficiency
Hyperthyroidism
Hyperparathyroidism
Bone marrow failure/infiltration

Chemotherapy, radiation, medications,
toxins
Infections
TB
Epstein-Barr virus
HIV
Parvovirus
Malignancies
Metastatic (e.g., breast, prostate, lung)
Leukemia/lymphoma
Multiple myeloma
Myelofibrosis
Paroxysmal nocturnal hemoglobinuria,
which can present as myelofibrosis or
acute leukemia
15
I SIGNS & SYMPTOMS
Collagen vascular disease

Acute/chronic infections
Bacterial
TB
Hepatitis C
HIV
Malignancies
Chronic granulomatous
diseases (e.g., sarcoidosis)
Renal disease
16
Table 6 (continued)
Inflammatory states/
anemia of chronic
disease
Renal disease
Hypometabolic/hypermetabolic states
Bone marrow failure/infiltration

Aplastic anemia:
Idiopathic
Fanconi anemia (autosomal recessive
disorder presenting with severe
pancytopenia in 1st 2 decades of life)
Pure RBC aplasia, including DiamondBlackfan anemia (congenital form of pure
RBC aplasia appearing in childhood)
Graft-versus-host disease
Modified from Hillman RS, Ault KA. Hematology in clinical practice: a guide to diagnosis and management. 2nd ed. New York: McGrawHill; 1998. p. 62. Used with permission.
I SIGNS & SYMPTOMS

Table 7. Intravascular and Extravascular Hemolysis for
Normocytic Anemia
Intravascular
Blood transfusion: ABO mismatched transfusion
Bacterial/parasitic infections
Bartonellosis
Clostridial sepsis
Malaria
Mycoplasma pneumonia
Paroxysmal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria
Paroxysmal cold hemoglobinuria
Mechanical heart valves
Snake bites
Thermal burns
Extravascular
Autoimmune hemolysis
Warm-reacting (IgG) AIHA
Cold-reacting (IgM) AIHA
Bacterial and viral infections
Infectious mononucleosis
Malaria
Mycoplasma pneumonia
Drug-induced hemolysis
Glucose-6-phosphate
dehydrogenase deficiency
Autoimmune drug reactions
Hemoglobinopathies
Thalassemia syndromes
Sickle cell disease
Membrane structural defects
Hereditary spherocytosis
Hereditary elliptocytosis
Acanthocytosis
Others
Disseminated intravascular
coagulation
Thrombotic thrombocytopenic purpura
Hemolytic uremic syndrome
Eclampsia (HELLP
syndrome)
AIHA, autoimmune hemolytic anemia; HELLP, hemolytic anemia, elevated

liver function tests, low platelets.
Modified from Hillman RS, Ault KA. Hematology in clinical practice: a
guide to diagnosis and management. 2nd ed. New York: McGraw-Hill;
1998. p. 187-8. Used with permission.
17
18
Table 8. Serum Profiles of Selected Anemias
Marrow
damage
RBC mor- Normolytic/
phology
normochromic
RI
<2
Serum
N1/increased
iron
TIBC
N1
Serum
Increased
ferritin
% Satura- 30-50
tion
Acute/
chronic
inflammatory
Renal
disease
Hypometabolic Thalasstates
semia
Iron deficiency
Hemoglobinopathy
Macrocytic
Dys- Sidero- Chronic
anemia plastic blastic hemolytic
Normocytic/ Normocytic Variable Microcytic/

hypochromicrocytic
mic
<2
<2
<2
<2
Decreased
N1
N1
N1/increased
Decreased
N1
N1
N1
Increased
N1
N1
>100 g/L
Normocytic/ Normocytic/ Macrocytic/ Mixed Mixed

microcytic/
normochro- normohypochromic mic
chromic
<2
>3-5
<1
<2
<2
Decreased
N1/increased Increased
N1
Increased
Increased
<10 g/L
N1
>100 g/L
N1
Increased
N1
N1
10-20
<10
NA
>50
NA
N1
N1
>20
NA, not applicable; N1, normal; RI, reticulocyte index; TIBC, total iron-binding capacity.
Normocytic/
normochromic
>3-5
N1
N1
N1
N1/inN1/increased creased
NA
NA
I SIGNS & SYMPTOMS

Table 9. Clues in the Peripheral Smear to the Diagnosis
of Anemia
Peripheral smear finding
Differential diagnosis
Lead poisoning, -thalassemia,

megaloblastic anemia, sideroblastic
anemia
Bite cells
G6PD
Blasts
Leukemia
Burr cells
Uremia
Heinz bodies
G6PD
Howell-Jolly bodies
Hyposplenism, megaloblastic anemia
Hypersegmented neutrophils Vitamin B12 and/or folate deficiency
Rouleau formation
Multiple myeloma
Schistocytes
TTP, HUS, HELLP syndrome, DIC,
collagen vascular disease, heart
valve hemolysis
Spherocytes
Hereditary spherocytosis, autoimmune hemolytic anemia, severe
burns
Spur cells (acanthrocytes)
Chronic liver disease
Target cells
Liver disease, thalassemia
Teardrop cells (dacrocytes) Myelofibrosis
Basophilic stippling
DIC, disseminated intravascular coagulation; G6PD, glucose-6-phosphate

dehydrogenase deficiency; HELLP, hemolytic anemia, elevated liver function tests, low platelets; HUS, hemolytic uremic syndrome; TTP, thrombotic
thrombocytopenic purpura.
TESTS AND WORK-UP

After a thorough history and physical exam, all anemia evaluations should include hemoglobin level, hematocrit, mean
cell volume, reticulocyte count, and a peripheral blood smear.
Specimens for a peripheral blood smear and reticulocyte
count should be drawn before blood transfusions unless the
clinical situation warrants emergent transfusion.
The reticulocyte count should be converted to the reticulocyte index (RI).
RI = % reticulocyte (patient hematocrit/normal hematocrit)
The RI is divided by 2 if nucleated RBCs are present.

Most cases of anemia are diagnosed with this basic approach.
If not, this approach usually suggests the next steps.
19
20
Hb <12 g/dL women or <13 g/dL men
Microcytic anemia (MCV <80 fL)

Serum ferritin, TIBC
Ferritin low
TIBC high
Ferritin normal or high

TIBC normal or decreased
Iron deficiency anemia
RBC and RDW
Look for a source

(see Table 4)
RBC <5x1012/L
RDW >15%
Any history of chronic disease:
consider anemia of chronic
disease
Does not fit any profile and

bleeding source ruled out:
consider hematology consult
and/or bone marrow biopsy
RBC >5x1012/L
RDW normal
Consider thalassemia
syndromes
Fig. 1. Algorithm for the

diagnosis of microcytic anemia. Hb, hemoglobin; MCV,
mean corpuscular volume;
TIBC, total iron-binding
capacity; RDW, red cell distribution width.
I SIGNS & SYMPTOMS

MANAGEMENT
Management of anemia includes the treatment of the underlying cause of the anemia. Two special circumstances are considered.
Iron Deficiency Anemia
After the underlying source of iron deficiency anemia is
addressed, oral supplement with iron is the treatment of
choice.

Normocytic anemia (MCV 80-100 fL)
RI
_
RI <2%
RI >2%
Any evidence of
early/acute blood loss?
Yes
No
Address
blood loss
Any evidence of renal

disease, chronic disease,
inflammatory states,
hypo/hypermetabolic
states (see Table 6)?
No
Peripheral smear, indirect bilirubin,

LDH to rule out hemolysis
No evidence of
hemolysis on smear,
normal indirect
bilirubin & LDH
Evidence of hemolysis
smear (see Table 9),
increased indirect
bilirubin & LDH,
decreased haptoglobin
Consider blood loss

Urine hemosiderin to
differentiate intravascular
vs. extravascular
hemolysis
Possible bone marrow

failure/infiltration (see
Table 6)
Consider bone marrow
biopsy and/or hematology
consult
Positive urine hemosiderin
Intravascular hemolysis
(see Table 7)
Negative urine hemosiderin
Extravascular hemolysis:
obtain Coombs test
See Table 7
Fig. 2. Algorithm for the diagnosis of normocytic anemia. Hb, hemoglobin; MCV, mean corpuscular volume; RI, reticulocyte index.
21
22
Macrocytic anemia (MCV >100 fL)

Vitamin B12/folate, TSH, liver
function tests: bilirubin, AST,
ALT, alkaline phosphatase
Respective tests positive
Tests negative
Differential diagnosis:
Vitamin B12/folate
deficiency
Hypothyroidism
Liver disease
Alcohol abuse
See Tables 2 and 5
Fig. 3. Algorithm for the diagnosis of macrocytic anemia.

Hb, hemoglobin; MCV, mean corpuscular volume; TSH, thyroid-stimulating hormone.
I SIGNS & SYMPTOMS
Ferrous sulfate, 325 mg orally 3 times daily, is given 1 hour

before or 2 hours after a meal.
For better absorption, ascorbic acid 250 mg can be given
with the ferrous sulfate.
Check CBC in 4 weeks.
Six months of treatment should replenish the iron stores.
Indications for RBC Transfusion

In most cases, RBC transfusion is not indicated for hemoglobin >10 g/dL.
RBC transfusion is indicated for hemoglobin <7 g/dL. Two
units of RBCs should be given to those who are stable. Some
patients may need more units of RBCs depending on the
rate of ongoing blood loss.
It is unclear if RBC transfusion is warranted for patients
with hemoglobin of 7-10 g/dL. RBC transfusions may be
beneficial for patients with myocardial ischemia who have
hemoglobin <10 g/dL and/or hematocrit 30%.
Patients >65 years and/or who have cardiovascular or respiratory disease (e.g., COPD) may not tolerate anemia. These
patients may benefit from RBC transfusions if hemoglobin
<8 g/dL.
23
I SIGNS & SYMPTOMS

BACK PAIN
A. Scott Keller, M.D.
Jay Smith, M.D.

Rapidly assess the patient: vital signs, history (predisposing
factors), physical exam.
Abdominal Aortic Aneurysm Rupture
Classic triad of abdominal or back pain, hypotension, and
pulsatile abdominal mass (usually left of midline and above
umbilicus)
Signs and symptoms of shockhypotension, tachycardia, mental status change
May lead to spinal cord infarction or death if rupture occurs
Pulses or blood pressure may be unequal in upper vs. lower
extremities or in left vs. right lower limb.
Consider the historyage, hypertension, atherosclerosis,
peripheral vascular disease, known abdominal aortic
aneurysm with recent expansion and/or diameter >5 cm,
spontaneous symptom onset, use of anticoagulants.
Aortic Dissection
Spontaneous onset of acute, severe, tearing pain in the chest
and/or interscapular region
Pain may last hours and often requires high doses of analgesia.
Pain is unrelated to position, but it may wax and wane.
Patient may have associated syncope, weakness, or paralysis from spinal cord ischemia.
Patient may have hypertension or hypotension and pulses or
blood pressure may be unequal in upper vs. lower or left vs.
right extremities
Pulses may be absent.
Patient may have new-onset aortic regurgitation, pulmonary
25
edema, or neurologic deficits.

Consider the historyspontaneous onset, age, hypertension,
cystic medial necrosis, Marfan syndrome, congenital bicuspid valve, coarctation, third-trimester pregnancy, history of
blunt chest trauma (e.g., motor vehicle accident).
Cord Compression (Due to Trauma, Tumor, or Infection)

Pain is localized to back and/or lower limb, worsens with
movement, coughing, sneezing, or straining (Valsalva effect).
Patient may have Lhermitte phenomenon, a shock-like
sensation along the spinal cord precipitated by head flexion.
Exam often reveals spinal percussion tenderness, upper
motor neuron signs, and possibly a sensory level.
If the conus medullaris or cauda equina is involved, lower
motor neuron findings may be present, including dermatomal deficits.
Patient may have bladder/bowel difficulties
Pain from traumacaused by contact or heavy lifting; may
involve disk herniation, fracture with bony impingement
(e.g., osteoporosis), or epidural hematoma
Pain from tumor
History of cancer suggests metastatic spine involvement
until proved otherwise.
Tumor is suggested by lack of comfortable position or by
increased pain when supine or at nighttime.
Pain from infection (epidural abscess)
Classic triad of pain (along spine or leg), fever, and weakness; rapidly progressive
Consider the history of immune system compromise
diabetes mellitus, renal failure, alcoholism, malignancy, IV
drug abuse, HIV, prolonged steroid use.
Also consider other infections (skin, vertebral osteomyelitis,
decubitus ulcer, spinal surgery, pyelonephritis); most are due
to Staphylococcus aureus; streptococcal organisms and
gram-negative bacilli are other common causes.
ADDRESSING THE RISK

See Table 1.
See Table 2.
26
Table 1. Addressing the Risk

Condition
Abdominal
aortic aneurysm rupture
Aortic dissection
Vital signs
Hypotension, unequal
pulse/blood pressure
upper vs. lower limbs
Hypertension or
hypotension, loss
of pulses
TEE, transesophageal echocardiography.
Exam findings
Treatment
Severe pain in
abdomen, back,
flank(s), shock
Acute tearing
pain in chest and/or
interscapular area
Pulsatile abdominal
mass
Two large-bore IVs of normal saline,

blood, emergency surgery consult
Dont waste time on tests!
If hypertensive, give IV -blocker
(pulse 60), sodium nitroprusside
If hypotensive, IV fluid & blood, TEE, CT
Emergency surgical consult
Back pain, usually

aggravated by
coughing or straining
Weakness/numbness
of legs, bladder or
bowel disturbances
Loss of or unequal
pulses/blood pressure
Aortic regurgitation,
pulmonary edema,
neurologic findings
Localized spinal
tenderness, lower
motor neuron &
dermatomal deficits
Emergency spine surgery consult and

analgesics
CT, MRI, possibly lumbar puncture
Surgery if trauma, dexamethasone and
surgery if tumor, IV antibiotics & surgery
if infection
27
I SIGNS & SYMPTOMS
Cord compresFever (if infection or

sion (trauma,
tumor), otherwise may
tumor, epidural be normal
abscess)
Symptoms
Table 2. Differential Diagnosis

Gastrointestinal
Bowel disorder
Gallbladder disease
Pancreatic disease
Peptic ulcer
Gynecologic
Ectopic pregnancy
Endometriosis
Ovarian cyst or tumor
Ovarian torsion
Pregnancy
Tubo-ovarian abscess
Hematologic
Sickle cell crisis
Infectious
Diskitis
Epidural abscess
Herpes zoster
Meningitis
Myelitis
Osteomyelitis
Pneumonia
Prostatitis
Sacroiliitis
TB (Pott disease)
Urinary
Metabolic
Hyperparathyroidism
Osteomalacia
Osteoporosis
Paget disease
Psychiatric
Anxiety
Depression
Functional/malingering
Substance abuse
Renal
Infection
Polycystic kidney
Renal vein thrombosis
Stone
Tumor
28
Rheumatologic
Ankylosing spondylitis
Polymyalgia rheumatica
Psoriatic arthritis
Reiter syndrome
Rheumatoid arthritis
Spinal
Arachnoiditis
Disk herniation
Osteoarthritis
Spinal stenosis
Spondylolysis
Spondylolisthesis
Primary tumor
Metastatic tumor
Trauma
Vertebral fracture
Traumatic spondylolysis
Osteoporotic compression
fracture
Musculoskeletal/ligamentous
strain
Vascular disease
Abdominal aortic aneurysm
rupture
Aortic dissection
Pulmonary embolism
Spinal cord infarction
(anterior spinal artery)
Other
Diffuse idiopathic skeletal
hyperostosis
Fibromyalgia
Pericarditis
Pleural effusion
Pyriformis syndrome
Retroperitoneal fibrosis,
hemorrhage, or mass
I SIGNS & SYMPTOMS

Gastrointestinal
Bowel disorders
Abdominal pain, possible radiation to back, nausea/vomiting, diarrhea or constipation, possible hematochezia or
melena
Abdominal X-ray, CBC, electrolytes, CT
May need upper and lower barium studies, colonoscopy
Gallbladder disease
Right upper quadrant pain (colicky postprandial if stones,
constant if cholecystitis), can be referred to right shoulder
(diaphragm irritation)
Altered bowel sounds, nausea/vomiting, Murphy sign
CBC, liver function tests, alkaline phosphatase, ultrasound
Pancreatitis or pancreatic cancer
Pain is epigastric and can radiate to back, often worse
when the patient is supine.
Nausea, vomiting, shock
Patient may have fever.
CBC, lipase, amylase, liver function tests, calcium, LDH,
lipids
Abdominal X-ray may show calcifications, CT most
helpful
Peptic ulcer perforation
Usually associated with epigastric pain
Can cause acute upper abdominal and back pain, shock,
peritoneal signs, decreased bowel sounds, rectal bleeding
(may be occult)
Abdominal X-ray to check for free air, CBC, amylase,
esophagogastroduodenoscopy, gastric lavage
Gynecologic
Usually low abdominal and/or pelvic pain
Pain may radiate to back if uterosacral ligament is involved.
Obtain history of sexual activity, sexually transmitted
diseases (including salpingitis), birth control, and menstruation.
29
Perform gynecologic and abdominal exam.

Fever can indicate infection.
Hypotension/shock, vaginal bleeding, and amenorrhea can
imply ruptured ectopic pregnancy.
CBC, -human chorionic gonadotropin, blood cultures if
infection, pelvic/transvaginal ultrasound or pelvic CT
Hematologic (Sickle Cell Disease)

Back pain may be due to acute sickle crisis with bone
ischemia/infarct, osteomyelitis (S. aureus, E. coli, Salmonella),
or vertebral compression from bone marrow hyperplasia
with cortical thinning.
CBC, blood cultures, X-rays
Fluid hydration, analgesia, oxygen as needed, appropriate
antibiotics as necessary
Infectious
History of IV drug use, urinary tract infection, skin infection
(including herpetic lesions), previous back surgery
Back pain plus fever; patient may have progressive neurologic involvement
CBC, ESR, C-reactive protein, blood cultures, empiric
IV antibiotics (vancomycin, nafcillin)
CT/MRI, plain X-rays
May need biopsy to confirm organism
Infectious or inflammatory myelitis can present with focal
neck or back pain with progressive neurologic involvement.
Causes include herpes zoster, Cytomegalovirus, herpes
simplex, Epstein-Barr virus, rabies, or schistosomiasis.
Can be associated with systemic lupus erythematosus,
Sjgren disease, Behet disease, and sarcoidosis
MRI of spine and brain with gadolinium
CSF usually shows mononuclear pleocytosis, PMNs may
be present, protein levels may be elevated.
Metabolic
May be chronic pain or acute onset from fracture
Patient may have radicular symptoms or signs if there is
neural compression.
Check X-rays, alkaline phosphatase, calcium, phosphate, and
25-hydroxyvitamin D. May check parathyroid hormone.
30
I SIGNS & SYMPTOMS

Check creatinine, sodium, and potassium
Osteomalacia = poor quality bone25-hydroxyvitamin D is
low, alkaline phosphatase is increased, calcium is low or
normal, phosphate may be low, urinary calcium is low; bone
biopsy is diagnostic
Osteoporosis = low-density boneserum calcium and phosphate generally normal
Phosphate can be increased if postmenopausal; alkaline
phosphatase can be increased if recent fracture.
Check bone density and metabolic screen for reversible
causes.
Paget disease = chaotic bone resorption and formation
alkaline phosphatase is increased, but calcium and phosphate are normal; urinary pyridinoline collagen cross-links
are increased.
X-rays show mixed areas of sclerosis and lysis (also seen
in some bone tumors).
Psychiatric
Past history of mental illness (depression, anxiety, psychosis),
substance abuse, or childhood abuse. Always rule out true
pathology!
Waddell signs suggest significant psychologic distress rather
than true pathology; consider psychologic/psychiatric referral if 3 of 5 tests are positive, although some may be seen in
neuropathic pain.
Waddell signs can be remembered by acronym TORDS:
tenderness, overreaction, regionalization, distraction, and
simulated tests.
Superficial tenderness or deep pain over entire lumbar
area when skin is lightly pinched/rolled.
Overreaction is disproportionate verbalization and expression.
Regionalization involves nonanatomic pain, weakness, or
give-way weakness during test but normal strength spontaneously.
Distracting tests produce discordant findings, such as no
back pain when patient is sitting and knee is extended,
31
but severe back pain with supine straight leg raise.

Simulated tests give the appearance of checking for pathology but should not elicit back pain. Two such tests are
axial loading (pressing downward on standing patients
head) and rotation (when the shoulders and pelvis are passively rotated in the same plane while the patient stands
relaxed with feet together).
Renal
Can cause abdominal, flank, or back pain along with hematuria
Stones and infections can cause urinary frequency, urgency,
and dysuria.
Stone pain is usually colicky and may radiate into groin.
Ultrasound or pelvic CT, CBC, urinalysis, and urine culture
Blood cultures if fever
Infection and renal vein thrombosis can cause fever.
Thrombosis can lead to hemorrhagic infarct, causing hypovolemia, shock, and poor renal function.
Check for elevated LDH and alkaline phosphatase.
Hypertension occurs in cases of bilateral thrombosis.
Elderly patients may have pulmonary emboli.
Tumors may cause back pain from local invasion or spinal
metastasis; tumor mass and polycystic kidneys may be palpable.
Rheumatologic
All may have elevated ESR, most respond to NSAIDs and/or
corticosteroids.
Symmetric, deforming joint involvement, prolonged morning stiffness
Anemia, usually positive rheumatoid factor, may have
rheumatoid nodules
Treat with guided exercise, rest, NSAIDs; may need azathioprine, hydroxychloroquine, or methotrexate
Reiter syndrome
Low back pain from sacroiliitis, tenderness of Achilles
tendon insertion, uveitis, urethritis, and sausage digits
Ask about recent bowel or genitourinary infections
(Campylobacter, Chlamydia, Salmonella, Shigella, Yersinia).
32
I SIGNS & SYMPTOMS
Psoriatic arthritis
Asymmetric arthritis, psoriasis, sausage digits
May precede or follow skin lesions
Check scalp, gluteal cleft, and umbilicus.
Young adults, M>F
Gradual onset low back pain that limits mobility because
of sacroiliitis
Prolonged morning stiffness that improves with exercise
Bamboo spine and sacroiliac erosions (fusion in later
stages) on X-ray
Patient may have elevated ESR, usually has HLA-B27
(but so do 7%-8% of normal population).
Painful muscles worse with movement, leading to apparent (not true) weakness. CK is usually normal.
Morning stiffness and inexplicable shoulder and hip girdle
pain, may have headache, jaw claudication, visual changes
if associated with temporal arteritis
If visual changes occur, treat immediately with steroids to
prevent blindness.
May have systemic symptoms such as fever, malaise, and
weight loss
Spinal Disorders
Arachnoiditis
Inflammation and fibrosis of arachnoid layer of spinal
meninges
Severe back and radicular pain; may fluctuate in intensity and distribution and result in weakness
May be idiopathic or follow subarachnoid hemorrhage,
meningitis, trauma, surgery, intrathecal injections; limited treatment options
Exam consistent with mixed mechanical-radicular syndrome
MRI shows clumping of nerve roots in cauda equina or
empty thecal sac (nerve roots stuck to periphery of thecal
sac).
33
34
Disk herniation
Usually, but not always, related to traumatic event
Pain often begins in lower back and radiates to buttocks and
into leg(s) below knee.
S1 radiculopathy may manifest as buttock pain only, without distal radiation.
Pain may be worse in leg than back; it is increased with sitting, straining, coughing, and forward flexion.
Patient may lean (sciatic scoliosis) and have muscle
spasm, myotomal weakness, dermatomal sensory deficit,
and reflex loss.
Straight leg raise may be positiveleg pain produced
when extended lower limb is passively raised while patient
is supine. It is more specific if symptoms occur at <60
of straight leg raise.
Crossed straight-leg raise occurs when contralateral leg
is raised and symptoms are reproduced in the symptomatic leg; this is not sensitive but very specific for mass
lesions (e.g., lumbar disk) causing radiculopathy.
Cauda equina syndrome is a surgical emergency and manifests as asymmetric leg weakness or sensory loss (including perianal area), variable areflexia, and bowel/bladder
dysfunction; X-rays usually show osteoarthritis, MRI is test
of choice when necessary.
Osteoarthritis
Pain worsens with activity, resolves with rest
Brief morning stiffness, gelling, local tenderness, crepitus
X-rays exclude other important osseous problems, but
radiographic osteoarthritis is not always symptomatic.
Spinal stenosis
Low back pain, motor weakness, and pseudoclaudication
(leg numbness or aching when walking, relieved with rest,
but normal pedal pulses)
Pain is aggravated by extension of lumbar spine and
relieved by flexion and rest.
Spinal stenosis may occur centrally (as described above)
or laterally, causing radicular symptoms with pseudoclaudicatory features.
X-rays usually show osteoarthritis; MRI is diagnostic of
structural stenosis, but structural stenosis not always symptomatic.
I SIGNS & SYMPTOMS
Spondylolysis (stress fracture of the pars interarticularis,

usually at L5-S1)
Low back pain, worse with standing or extending
Stork teststanding on one leg and extending may produce pain on that side.
X-ray may show fracture up to 70% of time; oblique views
are more sensitive.
Bone scans and CT (thin cut with contiguous slices) are
very sensitive; MRI is less sensitive.
If bilateral, spondylolysis may develop into spondylolisthesis.
Spondylolisthesis (forward slippage of one vertebra over
another)
Low back pain, typically worse with extension and standing
May result in lumbar or sacral radiculopathy because of
stenosis caused by the slippage
May present as radiculopathy similar to disk herniation
or root level pseudoclaudication as in stenosis
Symptoms typically are relieved with flexion, sitting, or
lying supine.
Exam may show step-off deformity at spinous process
because of forward slip, muscle hypertonicity, positive
stork test (see spondylolysis), or neurologic signs if radiculopathy is present.
Can be isthmic (result from spondylolysis) or degenerative
(usually at L4-5 and result from disk degeneration and
facet joint laxity allowing slippage)
X-rays are diagnostic of spondylolisthesis; MRI may be
needed to determine if stenosis exists; flexion-extension
X-rays may show instability if the segment is hypermobile.
Trauma
Suggested by history, local tenderness
Musculoskeletal or ligamentous strain is the most common
cause of acute low back pain. Patient may have paraspinal
muscle tenderness and spasm but not radicular signs or neurologic deficits.
35
Osteoporotic compression fracture is seen most commonly

in elderly white women. It is often seen with minimal trauma,
such as opening a window. X-rays confirm the diagnosis.
Vertebral fracture is usually from significant fall or motor
vehicle accident. X-rays confirm the diagnosis.
Tumor
Multiple myeloma is most common primary tumor.
Look for Bence Jones proteins in urine, check serum protein electrophoresis.
Other primary bone tumors, both benign and malignant, are
rare and primarily observed in younger patients (10-30
years).
Most metastatic tumors are in older patients.
If cauda equina or conus medullaris, treat urgently.
Cancer risk factors include age 50 years, history of cancer, unexplained weight loss, or failure to improve after 4-6
weeks of conservative therapy.
If none of these four risk factors is present, cancer can be
ruled out with virtually 100% sensitivity.
Main cancers that metastasize to bone are breast, lung, lymphoma, thyroid, kidney, and prostate.
If metastatic cancer, usually elevated ESR and alkaline
phosphatase (also acid phosphatase if prostate), calcium
may be elevated.
Vascular Disease
Ruptured aneurysm or dissectionhypotension, severe pain,
pulsatile midline mass, and loss of or unequal pulses; patient
may have new-onset aortic regurgitation.
Myocardial infarctionsubsternal chest tightness/pressure
radiating to left arm/axilla or jaw, diaphoresis, nausea,
dyspnea
Pulmonary embolismacute dyspnea, tachycardia, pleuritic pain
Spinal cord infarction (anterior spinal artery)acute-onset
pain, sparing of posterior columns, sharply demarcated cord
level
Other
Diffuse idiopathic skeletal hyperostosis causes spinal stiffness
36
I SIGNS & SYMPTOMS
and mild pain; X-rays show osteophyte formation and calcification of anterior longitudinal ligament and peripheral
disk margins.
Fibromyalgia is characterized by widespread musculoskeletal
pain, stiffness, paresthesia, easy fatigability, nonrestorative
sleep, and multiple symmetric tender points; it mainly affects
women.
Pericarditis may cause chest pain or pain radiating to back;
it typically improves when patient leans forward.
Pleural effusion may cause back or pleuritic pain.
Pyriformis syndrome typically has pain and tenderness in
buttock, may radiate down leg, but back pain is rare; worse
when sitting; may be confused with L5-S1 radiculopathy
Retroperitoneal fibrosis or hemorrhage
Fibrosis may be the cause of back pain in patients with a
history of retroperitoneal injury, surgery, methysergide
use, or radiation.
Consider hemorrhage in a patient with acute-onset lumbar
pain who takes anticoagulants.
TEST ORDERING
Urgent assessment required if fever >38C for 48 hours,
unrelenting night pain, pain with weakness or numbness
below knee, leg weakness, loss of bowel or bladder control,
progressive neurologic deficit, hypotension/shock; consult the
appropriate service.
Back pain with fever and rapidly progressive weakness
CBC, ESR, C-reactive protein, urinalysis, blood cultures,
amylase, lipase, lipids
CT or MRI
Back pain, hypotension
Call surgery
Chest/abdominal X-ray (free air), ultrasound, CT, or
aortogram
Tearing back pain in chest radiating to interscapular region
CBC, chest X-ray, ECG
Transesophageal echocardiogram or CT, possible
aortogram
37
History of cancer, age >50 years, insidious onset of pain,

weight loss, pain at rest
Spinal/chest X-rays, mammogram
CBC, ESR, alkaline phosphatase, calcium, phosphate,
prostate-specific antigen, thyroid-stimulating hormone,
vitamin D, Bence Jones protein, serum protein electrophoresis
CT or MRI, possible bone scan
Back pain with recent trauma
Spinal X-rays
Possible CT or MRI
Back pain with radicular pain
MRI
Possible EMG
MANAGEMENT OF THE MOST COMMON CAUSES OF

ACUTE BACK PAIN
Musculoskeletal
Gentle range-of-motion exercises (bedrest 1-2 days if not
able to ambulate because of pain)
NSAIDs
Gradual resumption of daily activities
Muscle relaxants (e.g., cyclobenzapine [Flexeril] or baclofen)
may be used initially but may cause sedation.
Narcotics are rarely indicated.
Osteoarthritis
NSAIDs
Intra-articular (facet joint) corticosteroid injections may be
useful.
Regular exercise is beneficial (avoid overuse), as are heating
pads or warm baths, weight reduction, and physical therapy.
Lumbosacral corset may provide symptomatic relief.
Can lead to radicular symptoms, cauda equina compression
syndrome, spinal stenosis, disk herniation, and spondylolisthesis
Disk Herniation
If nonprogressive radicular pain, initial nonsurgical treatment for 6 weeks allows inflammation to subside: pain
resolves in 90% of patients.
38
I SIGNS & SYMPTOMS
Treatment is same as for musculoskeletal pain.

Epidural injections of corticosteroids can provide temporary relief.
If pain does not resolve or if rapidly progressive neurologic
deficits occur, surgery is indicated.
39
I SIGNS & SYMPTOMS

BLEEDING DISORDERS
Thomas P. Worley, M.D.
John A. Heit, M.D.
Rajiv K. Pruthi, M.B.B.S.
If the following abnormalities exist, call for backup and do
not let the diagnostic work-up delay stabilization of the
patient:
Vital signstachycardia, hypotension
General appearancepallor, cold and clammy appearance
Mental status changes or confusion
Obvious large bleeding site
Bleeding from numerous sites
ADDRESSING THE RISK
For serious or life-threatening bleeding
Secure the airways.
Obtain venous accesstwo large-bore peripheral IVs.
Start fluid resuscitation with 0.9 isotonic saline, and order
emergency RBCs.
Give nasal oxygen if intubation is not necessary.
Obtain a priority type and crossmatch, CBC, aPTT, PT, and
fibrinogen to assess the degree of bleeding and to screen
for coagulopathy.
Evaluation
Mental status changes, thrombocytopenia, hemolytic anemia, fever, and renal failure are indicative of thrombotic
thrombocytopenic purpura.
Confirm with a peripheral blood smear (presence of
schistocytes).
Treatment should be started immediately (see below).
In a bleeding patient, specific-component replacement
therapy depends on the underlying coagulation abnormality.
Special abbreviation used in this chapter: IVIg, intravenous immunoglobulin.

41
Results of laboratory tests are not always available immediately; thus, it is important to assess the patient clinically,
taking into account the patients previous history (e.g.,
liver disease, malignancy) and medication use.
In the absence of signs and symptoms for thrombotic
thrombocytopenic purpura, replenishment with fresh
frozen plasma, cryoprecipitate, and platelets should be
considered.
In a patient with bleeding from multiple sites, an increase
in aPTT and PT, and thrombocytopenia, consider acute
disseminated intravascular coagulopathy.
Initiate a diagnostic work-up for potential causes.
For patients receiving anticoagulation (heparin or warfarin) or with a known plasma coagulation disorder, attend
to the following potential life-threatening issues:
New neurologic deficitsrule out central nervous system bleeding (CT of head).
New onset of back pain or radicular painrule out
retroperitoneal hematoma (CT of abdomen).
Bleeding disorders can be classified into the following four
main categories:
Platelet disorders (Table 1)
Vascular disorders (Table 2)
Plasma coagulation disorders (Table 3)
Mixed disorders (Table 4)

In the hospital, abnormal bleeding is often due to the patients
underlying disease or treatment of the disease. The history
and physical exam should focus on identifying the following
common causes:
Liver disease, splenomegaly, uremia
Anticoagulation, chemotherapy administration
Recent procedure (surgery, biopsy) that would be a source
of bleeding
Common reasons for initiating a bleeding disorder work-up
History indicative of more bleeding than expected for a
hemostatic challenge
Spontaneous bleeding
42
I SIGNS & SYMPTOMS

Physical manifestations of bleeding
Lab abnormalities
Determine the type of bleeding (Table 5) and the onset of
bleeding (Table 6) to formulate a suggested abnormality.
Physical exam findings will suggest a diagnostic category
and guide further testing (Table 7).
Table 1. Platelet Disorders

Quantitative platelet disorders (thrombocytopenia)
Decreased production or bone marrow failure
Aplastic anemia
Myelofibrosis
Leukemia
Metastatic marrow infiltration
Viral infectioninfluenza, hepatitis, rubella, HIV
Myelosuppressionradiation, toxic agents, drugs,
chemotherapy
Vitamin B12, folate deficiency
Congenital thrombocytopenias
Decreased survival and increased destruction
Immune mediated
Idiopathic thrombocytopenic purpura
Autoimmune secondary to rheumatic disease,
infection, malignancy
Drug-induced immune thrombocytopeniaheparin,
quinine
Post-transfusion thrombocytopenia
Nonimmune mediated
HELLP syndrome
Disseminated intravascular coagulation
Extracorporeal circulation
Prosthetic intravascular devices
Cavernous hemangioma
Splenic sequestration
Dilutional thrombocytopenia (after large amounts of fluid or
RBCs)
Artifactual thrombocytopenia (platelet clumping)
Type 2B von Willebrand disease
43
Table 1 (continued)
Qualitative platelet disorders
Congenital qualitative disorders
Bernard-Soulier syndrome (giant platelets)
Glanzmann thrombasthenia
Paraproteinemias
Uremia
Liver failure
Thrombocytosis
Medications
Antiplatelet drugsaspirin/NSAIDs, clopidogrel,
glycoprotein IIb/IIIa inhibitors
-3 fatty acids
Semisynthetic penicillins or cephalosporins
HELLP, hemolysis, elevated liver enzymes, low platelet count.
Table 2. Vascular Disorders

Congenital disorders
Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber
syndrome)
Cavernous hemangioma
Connective tissue disorders
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Pseudoxanthoma elasticum
Acquired disorders
Structural abnormalitiessurgical or procedural disruption,
ulcerations, polyps, bladder or uterine abnormalities
Scurvy
Immunoglobulin disorders
Cryoglobulinemia
Benign hyperglobulinemia
Waldenstrm macroglobulinemia
Amyloidosis
Glucocorticoid excess
44
I SIGNS & SYMPTOMS

Table 3. Plasma Coagulation Disorders
Hereditary disorders
Afibrinogenemia
Dysfibrinogenemia
Factor II deficiency
Factor VII deficiency
Factor XIII deficiency
Hemophilia A (factor VIII deficiency)
Hemophilia B (factor IX deficiency, Christmas disease)
Hemophilia C (factor XI deficiency)
von Willebrand disease
Acquired disorders
Anticoagulants
Factor X deficiency (seen in amyloidosis)
Factor VIII inhibitor (or other factor inhibitor)
Liver disease
Primary fibrinolysis
Uremia
Vitamin K deficiency
Table 4. Mixed Disorders

Liver failure
Uremia
Table 5. History of Bleeding Type and Associated

General Abnormalities*
Type of bleeding
Mucocutaneous bleeding (i.e.,
epistaxis), petechiae
Delayed, recurrent oozing from a
cut or surgical site; hematoma
formation, hemarthrosis
Menorrhagia, gastrointestinal
bleeding, hematuria, or central
nervous system bleeding
Disorder suggested
Platelet disorder or vasculitis
Plasma coagulation disorder
Both platelet & coagulation

defects; also must consider
structural abnormality
*Note: Epistaxis and menorrhagia are classically associated with von

Willebrand disease. Hemarthrosis is classically associated with hemophilia.
45
Table 6. History of Onset of Bleeding: Congenital

Versus Acquired Bleeding Disorders
Duration of
bleeding
Lifelong
Recent onset
Disorder suggested
Congenital defect; often of a single factor;
confirm with family history (bleeding or consanguinity), personal history of bleeding with
trauma, tooth extractions, circumcision, menses,
surgical procedures, history of iron responsive
anemia
Acquired disorder; usually affecting multiple
coagulation factors; confirm with history of no
lifelong excessive bleeding
Inquire about concurrent symptoms or medical
conditions, new medications (NSAIDs, aspirin,
semisynthetic penicillins, warfarin) & dietary
habits (vitamin K deficiency, ethanol use)
Table 7. Associated Physical Exam Findings

Physical exam finding
Dependent asymptomatic
petechiae
Palpable, pruritic petechiae in
clusters
Palpable purpura
Superficial bleeding
Deep hematoma
Hemarthrosis
Extensive superficial purpura
Splenomegaly
Skin or joint laxity
Telangiectasias
Palmar erythema, asterixis,
spider angiomata, gynecomastia
46
General disorder suggested

Thrombocytopenia
Vasculitis
Vasculitis
Thrombocytopenia or vascular
defect
Coagulation disorder
Coagulation disorder (classically
hemophilia)
Coagulation disorder
Platelet sequestration
Connective tissue disorder
Vascular disorder
Coagulopathy secondary to liver
disease
I SIGNS & SYMPTOMS

TEST ORDERING
All patients being evaluated for a bleeding disorder should
have the following:
CBC with differential
aPTT and PT
von Willebrand factor
Peripheral blood smear
Other more specific tests include thrombin time, fibrin degradation products, D-dimer, platelet aggregation studies, specific coagulation factor/inhibitor assays, and mixing studies.
Algorithms for evaluating patients with bleeding disorders and
findings suggestive of platelet or vessel wall abnormality,
or suggestive of an acquired plasma coagulation disorder,
or suggestive of a congenital plasma coagulation disorder
are given in Figures 1, 2, and 3, respectively.
INITIAL MANAGEMENT
Idiopathic Thrombocytopenic Purpura
Confirmation
Thrombocytopeniacheck peripheral blood smear for
clumping
Rule out other causes of thrombocytopenia.
Normal PT, aPTT, and fibrin degradation products
Lack of hemolyzed red cells on peripheral blood smear
Discontinue any drugs that may be causative.
No role for platelet transfusions unless patient is actively
bleeding or has platelet count <10,000/L (<10 109/L).
If bleedingprednisone, 1-2 mg/kg daily, and follow platelet
count
If refractory to corticosteroids or rapid correction of platelet
count is neededIVIg 0.4 g/kg daily infused 3-5 consecutive days
In cases of emergencyIVIg 1 g/kg and repeat in 24
hours.
If no response after 2-3 weeks of corticosteroids, consider
splenectomy.
47
48
Platelet count
Normal
Consider following causes:
Vascular disorder (skin biopsy)
Uremia
Paraproteinemia
Medicationsaspirin, NSAIDs,
synthetic penicillins
Platelet dysfunction
High
Thrombocytosis with secondary
platelet dysfunction or alternative
diagnosis
If above are not clinically evident,

consider vWD & platelet function
disorders
Check assays for factor VIIIc, vWF

antigen, ristocetin cofactor activity
Abnormal
vWD: multimer analysis and other
specialized testing to determine
subtype (which affects treatment)
aPTT may be prolonged due to
factor VIII deficiency
Normal
Consider congenital platelet
function/secretion abnormalities
Afibrinogenemia
Low
Examine peripheral blood smear
Platelet normal size

Consider the following causes:
Splenomegaly with sequestration
ITP
TTP
Anemia
Increased LDH
Schistocytes
Bone marrow failure (consider
causes)
marrow biopsy
DIC
check fibrin degradation
products & PT & aPTT
Drug-induced thrombocytopenia
(heparin, quinine)
Platelet clumping: artifact
Fig. 1. Evaluation of bleeding disorders with history and

physical exam suggestive of
platelet or vessel wall abnormality. DIC, disseminated
intravascular coagulation; ITP,
idiopathic thrombocytopenic
purpura; TTP, thrombotic
thrombocytopenic purpura;
vWD, von Willebrand disease;
vWF, von Willebrand factor.
Check aPTT & PT
Normal aPTT & PT

Subacute DIC
Vascular disorder
Increased aPTT
Acquired factor VIII inhibitor
(confirm with mixing studies)
Heparin administration
Lupus anticoagulant (not clinically
bleeding)
Increased PT
Liver disease
Warfarin
Dysfibrinogenemia
Fig. 2. Initial evaluation of bleeding
49
patients with history and physical exam

suggestive of an acquired plasma coagulation disorder. DIC, disseminated
intravascular coagulation.
Abnormal
DIC
Heparin
Primary fibrinolysis
Liver disease
Dysfibrinogenemia
Normal
Liver disease
Warfarin
I SIGNS & SYMPTOMS
Peripheral blood smear
Increased aPTT & PT

Check thrombin time, fibrin
degradation products,
fibrinogen
50
Check aPTT & PT
Normal aPTT & PT

Consider:
Factor XIII deficiency
Mild hemophilia
Increased aPTT
Consider:
Hemophilia A/B: check factor
VIII & IX assay
Severe vWD (evalulate for vWD,
Fig. 1)
Increased PT
Consider:
Factor VII deficiency
Factor II, V, X deficiency
Increased aPTT & PT

Consider:
Factor II, V, X deficiency
Afibrinogenemia or
dysfibrinogenemia
Fig. 3. Evaluation of bleeding patients with history and physical exam suggestive of a congenital plasma
coagulation disorder. vWD, von Willebrand disease.
I SIGNS & SYMPTOMS

Thrombotic Thrombocytopenic Purpura
Confirmationthrombocytopenia, anemia, schistocytes,
increased LDH, with/without mental status changes, fever.
Methylprednisolone, 1-2 mg/kg daily, in combination with
Plasma exchangeshould be initiated without delay, 2-3
L exchange/day with fresh frozen plasma
If plasma exchange is not immediately availabletransfusion with fresh frozen plasma until plasma exchange is
possible
Platelet transfusions are contraindicated.
Consider possible causesinfection, drugs, malignancy,
chemotherapy, bone marrow transplant, pregnancy, idiopathic
von Willebrand Disease
Most common congenital bleeding abnormality
Confirmation
With/without abnormal bleeding time
Decreased or normal von Willebrand factor antigen
Decreased or normal factor VIIIc
Decreased ristocetin cofactor activity
Specialized testing is needed to establish type of von Willebrand
disease, and treatment should be based on the type.
On diagnosis, a trial of desmopressin acetate (DDAVP)
should be considered except for patients with type 2B von
Willebrand disease (in whom it is contraindicated) or type 3
(in whom it is ineffective).
Without previously established efficacy for the individual
patient, desmopressin acetate should not be the first therapy
of choice for management of bleeding in von Willebrand
disease.
von Willebrand disease type 1 and types 2A, 2N, and 2M
(spontaneous bleeding or surgery)
Desmopressin acetate 0.3 g/kg infusion in 50 mL of
saline over 30 minutes, may be repeated every 12 to 24
hours (note that rapid tachyphylaxis and syndrome of
inappropriate antidiuretic hormone with hyponatremia
and seizures can develop with subsequent doses if repeated within 24 hours)
51
If desmopressin acetate is ineffective, treat with factor

VIIIvon Willebrand factor concentrate as below.
von Willebrand disease types 2A, 2B, 2M, and 3 (spontaneous bleeding)
Factor VIIIvon Willebrand factor concentrate 20-30 IU/kg
Cryoprecipitate should be avoided, but it can be used in
case of emergency if factor VIIIvon Willebrand factor
concentrate is not available.
Monitor factor VIII coagulant levelsgoal factor VIIIc,
>30 IU/dL
Before a major operation, increase dose to 40-60 IU/kg
per day with a goal factor VIIIc >50 IU/dL until healing
is complete.
Hemophilia A (Factor VIII Deficiency)

Confirmation
Male patient
With/without a bleeding history or family history
Increased aPTT
Decreased factor VIII assay (<0.5 U/mL)
Life-Threatening Bleeding
Replace the deficient factor VIII, available as recombinant
products (rFVIII) or as purified plasma-derived products
(FVIII), 30-40 U/kg infusion repeated every 12 hours
Goal plasma factor VIII level, 80%-100%
Up to 50% of patients with hemophilia A may have factor VIII
inhibiting antibodies, treatment then must be recombinant
activated factor VII (rFVIIa), activated prothrombin coagulant complex (aPCC), or porcine factor VIII.
Minor Bleeding
Replace factor VIII, as above, with rFVIII or FVIII,
25 U/kg.
Goal plasma factor VIII level, 50%
In patients with mild hemophilia A, desmopressin acetate, 0.3
g/kg infusion over 30 minutes, may be sufficient to stop
minor bleeding.
Warfarin-Induced Coagulopathy
Confirmationhistory of warfarin use and increased INR
52
I SIGNS & SYMPTOMS

Life-Threatening Bleeding
Fresh frozen plasma, 15 mL/kg (goal INR, <1.5) for immediate and temporary correction of coagulopathy
or
Prothrombin complex concentrate, 25 U/kg
Requires less volume and has more rapid onset
Associated with slight risk of thrombosis
Vitamin K, 5-10 mg PO or by nasogastric tube
If unable to give enterally or malabsorption is present,
then vitamin K 1 mg IV over 60 minutes
Because of small risk of anaphylaxis, epinephrine should
be kept at the bedside.
NonLife-Threatening Bleeding or Asymptomatic
Increased INR
Vitamin K, 5-10 mg PO
If unable to take enterally or malabsorption is present,
give IV, as above.
If INR <5.0 and no evidence of bleeding, hold warfarin
and allow INR to correct without treatment while monitoring closely.
Note: After vitamin K administration and resumption of
warfarin therapy, it will take a longer time for INR to increase
to the targeted therapeutic range. Use of higher doses of
warfarin may result in overshooting target INR.
Acute Disseminated Intravascular Coagulation
Confirmation
Increase in PT, aPTT, thrombin time, fibrin degradation
products, D-dimer
Decrease in fibrinogen
Thrombocytopenia complexes
Increased soluble fibrin monomer complexes
Diagnose and treat the underlying cause (sepsis, hypoxia,
acidosis, malignancy).
Supportive care
Replacement of consumed coagulation factors (fresh frozen
plasma), fibrinogen (cryoprecipitate), and platelets
53
Liver Failure
Confirmation
Acute fulminant liver failureextreme prolongation of
PT, aPTT, and thrombin time, along with clinical scenario
Chronic liver failurevariable prolongation of PT, aPTT,
and thrombin time
Often associated with disseminated intravascular
coagulation
If the patient is not actively bleeding, give vitamin K, 5 mg
PO daily.
For acute bleeding episodes, give fresh frozen plasma, 20-30
mL/kg; however, use judiciously to avoid fluid overload.
For procedures (liver biopsy), give 2 units of fresh frozen
plasma immediately before the procedure.
Replace platelets if <50 109/L and fibrinogen if <75
mg/dL.
54
I SIGNS & SYMPTOMS

CHEST PAIN
Evaluate the general status of the patient:
Confusion and agitation suggest decreased cerebral perfusion.
Profuse diaphoresis signals adrenergic discharge as seen
in myocardial infarction, unstable angina, dissection, and
major catastrophes.
Hypotension, cyanosis, and low pulse oxymetry levels
suggest life-threatening conditions.
Tachycardia and tachypnea in the setting of pain are nonspecific.
If an abnormality is detected with this approach, consider
myocardial infarction, unstable angina, pulmonary embolism,
tension pneumothorax, aortic dissection, or arrhythmia.
Before proceeding with further evaluation, call for backup.
ADDRESSING THE RISK
Immediately rule out conditions whose treatment will most
imminently avert death:
Tension pneumothorax
Arrhythmia with hemodynamic instability
Tension pneumothoraxblood pressure measurement and
chest X-ray (see chapter on Chest X-ray)
ArrhythmiaECG (see chapter on ECG)
Tachyarrhythmias with hemodynamic instability require
immediate electrical cardioversion.
If patient is not coding, general measures to be undertaken
initially include
Oxygentry to ensure oxygen saturation of at least 90%.
Venous accessmake sure patient has a large-bore access
for eventual fluid resuscitation.
55
Monitor cardiac rhythm and blood pressure.

Let ICU know about the patient.
Differential Diagnosis
See Table 1.
Table 1. Causes of Chest Pain
Cardiovascular
Angina
Aortic dissection
Pericarditis
Aortic stenosis
Mitral valve prolapse
Tachyarrhythmias
Pulmonary
Pulmonary embolism
Pneumonia
Pneumothorax
Pleuritis
Gastrointestinal
Esophageal spasm
Esophagitis
Esophageal cancer
Hiatal hernia
Peptic ulcer disease
Gallbladder disease
Aerophagia
Musculoskeletal
Costochondritis (Tietze syndrome)
Radicular syndromes
Inflammatory syndromes
Sternum osteomyelitis
Rib fractures
Metastatic bone disease
Psychogenic
Panic attack
Conversion disorders
Other
Herpes zoster
Syndrome X
Intrathoracic tumors
Mondor disease
Differentiating the Differential

Classify chest pain as typical angina, atypical angina, noncoronary chest pain:
Typical anginadeep, crushing retrosternal discomfort
(usually not described as pain) of moderate to severe intensity; predictable with exertion, cold, or emotion; recurrent, lasting 3-20 minutes; relieved by rest or nitroglycerin;
with or without radiation to neck, arm, or jaw; may be
accompanied by nausea and diaphoresis
Atypical anginaa variation of the above in which the
pain may have a burning quality, may not always occur
with the same degree of effort or at rest, and may be
referred to other parts of the chest, such as left side; more
common in women
56
I SIGNS & SYMPTOMS
Noncoronary chest painusually well localized, sharp or

tearing in quality, lasts <3 minutes or several hours or days,
is unpredictable, nonreproducible with exertion, varying
severity, not usually relieved by nitroglycerin or rest
Risk factors, symptoms, and signs are listed in Tables 2, 3,

and 4, respectively.
Ordering Tests
All patients in the hospital with chest pain should have ECG,
chest X-ray, and oxymetry level (Table 5).
Initial Management of 7 Causes of Chest Pain

Uncomplicated Myocardial Infarction
(see chapter on Acute Coronary Syndromes)
Confirmation >1-mm ST-segment elevation on contiguous
ECG leads troponin rise CK-MB and CK enzyme curve
Management
Oxygen intranasally at 2-5 L/min
Aspirin 325 mg PO
Morphine 2-4 mg IV as needed for pain
Metoprolol 5 mg IV every 15 minutes until heart rate <60
beats/min
Thrombolysis or percutaneous coronary intervention
Troponin, CK, CK-MB, ECG every 6 hours
Unstable Angina
Confirmationnew chest pain or pain at rest wave inversion T wave or new ST-segment depressions
Management
Aspirin 325 mg PO
Nitroglycerin (patch, paste, or IV)
Heparin 5,000 IU IV bolus + infusion to target aPTT of
50-75 seconds
Metoprolol 5 mg IV every 15 minutes until heart rate <60
beats/min
Atorvastatin 80 mg PO or simvastatin 40 mg PO
57
Troponin, CK, CK-MB, aPTT, ECG every 6 hours

Emergency angiography and percutaneous coronary intervention of culprit flow-limiting lesion
Clopidogrel 300 mg PO unless emergency coronary artery
bypass graft is planned.
Pulmonary Embolism
Confirmationhigh-probability ventilation-perfusion scan,
thrombus seen on spiral CT or pulmonary angiography
Management
Heparin 5,000 IU IV bolus + infusion to target aPTT of 5075 seconds (if clinical suspicion is high, should not await
confirmation)
Thrombolysis if hemodynamically unstable
Thrombolysis if massive pulmonary embolism with right
ventricle failure and shock
aPTT every 6 hours
Chest X-ray daily
Arterial blood gases daily
Aortic Dissection
Confirmationflap seen on transesophageal echocardiography or chest CT
Table 2. Risk Factors

Age >60: MI, PE, aortic dissection, pneumonia, herpes zoster,
malignancy
Age <40: psyche, musculoskeletal, pneumothorax, pericarditis,
GERD
Hypertension: aortic dissection, MI
Female: psyche, gallbladder, aerophagia, syndrome X
Male: MI, PUD, aortic dissection
Tobacco: pneumonia, MI, PUD, malignancy
Postoperative: MI, PE, pneumonia, musculoskeletal
Alcohol: PUD, pneumonia, GERD
Obesity: PE, GERD, MI
Diabetes mellitus: MI, UA
Dyslipidemia: MI, UA, aortic dissection
Marfan syndrome: aortic dissection
GERD, gastroesophageal reflux disease; MI, myocardial infarction; PE,
pulmonary embolism; PUD, peptic ulcer disease; UA, unstable angina.
58
I SIGNS & SYMPTOMS

Table 3. Symptoms
Quality of the pain
Constrictive: MI, esophageal spasm, psyche
Burning: MI, UA, herpes zoster, GERD, PUD
Tearing: aortic dissection, esophageal rupture
Pleuritic: pleuritis, pneumonia, PE, pneumothorax, pericarditis
Sharp: musculoskeletal, Tietze syndrome, psyche, aortic
dissection, PUD, pneumothorax, rib fracture
Dull, steady: MI, UA, musculoskeletal, esophageal spasm,
PUD, pericarditis
Location
Retrosternal: MI, UA, esophageal spasm, GERD, aortic dissection
Sides: psyche, pneumonia, pleuritis, pneumothorax
Back: aortic dissection, pneumonia, pleuritis, pneumothorax
Duration
<1 min: probably nothing, psyche
5 min-20 min: stable angina, esophageal spasm, pneumothorax
>20 min-2 h: UA, MI, musculoskeletal, aortic dissection, PE
Several hours to days: musculoskeletal, GERD, pneumonia,
pericarditis, PUD, cancer
Radiation
Arms: MI, UA, stable angina, psyche
Neck: MI, UA, carotid dissection, cervical radiculopathy
Jaw: MI, UA
Back: aortic dissection, PE, pneumothorax, gallbladder
disease
Provocative factors
Exertion with lag: angina, UA, MI, aortic dissection
Exertion without lag: musculoskeletal, PE, esophageal spasm
Emotion: UA, MI, psyche
Breathing: pneumonia, pneumothorax, PE, pleuritis,
pericarditis
Vomiting: esophageal rupture
Chest palpation: Tietze syndrome, Mondor disease, rib
fracture, metastasis, osteomyelitis
Eating: esophageal spasm, GERD, PUD
Relieving factors
Rest with lag: angina
Rest without lag: musculoskeletal
Nitroglycerin: angina, UA, esophageal spasm
Antacids: GERD, PUD
Leaning forward: pericarditis
Shallow breathing: pneumonia, pleuritis
No relief: MI, PE, aortic dissection, pneumothorax
GERD, gastroesophageal reflux disease; MI, myocardial infarction; PE, pulmonary
embolus; PUD, peptic ulcer disease; UA, unstable angina.
59
Table 4. Signs
Hypotension
MI
Massive pulmonary embolism
Pneumonia with sepsis
Hypertension
Aortic dissection
Cyanosis
Pulmonary embolism
Pneumothorax
Myocardial infarction with
cardiogenic shock
Pneumonia
S3
Unstable angina
Aortic stenosis
Murmur
Unstable angina
Aortic stenosis
Distended neck veins
Right ventricular myocardial
infarction
Superior vena cava
syndrome
Pericardial rub
Pericarditis
Pleural rub
Pneumonia
Pulmonary embolism
Hamman sign
Esophageal rupture
Subcutaneous emphysema
Esophageal rupture
Abolished breath sounds
Pneumothorax with effusion
Hyperresonant percussion
Pneumothorax
Low oxygen saturation
Pulmonary embolism
Pneumothorax
Shock
Pneumonia
Vesiculopapular rash
Herpes zoster
Profuse diaphoresis
Aortic dissection
Pulmonary embolism
Pulse asymmetry
Aortic dissection

Labetalol IV infusion at 2 mg/min, titrate to systolic blood
pressure <110 mm Hg (initiation should not await confirmation)
or
Nitroprusside IV 2.5-5 g/kg per minute + propranolol 1
mg IV every 4-6 hours
Consult emergency cardiovascular surgery.
Pericarditis
Confirmationtransthoracic echocardiography with thickened pericardium and fluid
Management
NSAIDs PO
Pericardiocentesis for tamponade
60
I SIGNS & SYMPTOMS

Pneumothorax
Confirmationchest X-ray with air in the pleura
Management
Thoracocentesis or chest tube
Table 5. Diagnostic Test Ordering for Chest Pain (CP)

Findings
Diagnosis
Tests ordered
CP + diaphoresis + S3
murmur
Sharp/pleuritic pain +
low O2 sat + dyspnea
CP + dyspnea distended neck veins +
hypotension
Severe back pain +
hypertension
MI, unstable angina,

aortic stenosis
Pneumothorax, PE,
esophageal rupture
Pneumothorax, right
ventricle MI,
massive PE
Aortic dissection,
MI
Retrosternal CP +
vomiting +
diaphoresis
Restrosternal CP
related to meals
Any CP + CAD risk
factors
Acute dyspnea +
bilateral crackles
MI, unstable angina
ECG, enzyme curve,

echo, CXR
CXR, ABGs, spiral
CT or V/Q scan
CXR, ECG, enzyme
curve, echo, spiral
CT or V/Q scan
CXR, ECG, enzyme
curve, TEE or CT
thorax
ECG, enzyme curve
Esophageal causes,
PUD
MI, unstable angina
EGD, barium
swallow
ECG, enzymes
Pericardial rub
distended neck veins
Hypertension + pulse
asymmetry
CP + fixed distended
neck veins Horner
syndrome
MI with CHF,
ECG, CXR, enzyme
unstable angina,
curve
PE
Pericarditis, pleuritis CXR, ECG, echo
Aortic dissection,
CXR, TEE, CT
coarctation
thorax
Superior vena cava
CXR, CT thorax
syndrome, Pancoast
syndrome
ABG, arterial blood gas; CAD, coronary artery disease; CHF, congestive
heart failure; CXR, chest X-ray; echo, echocardiography; EGD, esophagogastroduodenoscopy; MI, myocardial infarction; O2 sat, oxygen saturation; PE, pulmonary embolus; PUD, peptic ulcer disease; TEE, transesophageal echocardiography; V/Q, ventilation-perfusion.
61
Esophageal Spasm/Reflux
Confirmationbarium swallow or esophagogastroduodenoscopy
Management
Omeprazole 40 mg PO
Maalox 20 mL PO
Esophagogastroduodenoscopy in AM
62
I SIGNS & SYMPTOMS

COUGH, HEMOPTYSIS, AND HICCUP
Douglas L. Riegert-Johnson, M.D.
Vanessa Z. Riegert-Johnson
Constance Jennings, M.D.
COUGH AND HEMOPTYSIS

Cough not associated with other comorbiditiesrarely life
threatening
Potentially life-threatening situations include
Massive hemoptysis >600 mL/24-48 hours or amount
sufficient to cause hemodynamic or respiratory compromise
Medical emergency (mortality rate, 38%)
Differential diagnosis: bronchiectasis, bronchogenic
pneumonia, TB, aspergillosis, necrotizing gram-negative pneumonia, endobronchial mass
Pneumothorax
ADDRESSING THE RISK

Massive Hemoptysis
Determine that blood has originated from the chest and not
the gastrointestinal or upper respiratory tract.
Ensure hemodynamic stability.
Position the patient semiupright with bleeding side down.
Consider emergent pulmonology consultation for emergent
bronchoscopy.
Consider emergent radiology consultation for emergent
bronchial artery embolization.
Consider chest CT if patient is stabilized.
Consider emergent thoracic surgery consultation if embolization is not successful.
Assess adequacy of airway; admister oxygen.
Special abbreviation used in this chapter: ACE, angiotensin-converting enzyme.

63
Order CBC, aPTT, PT, crossmatch; reverse anticoagulation

as needed.
Volume replacement as needed
Conservative management if due to bronchiectasis
Pneumothorax
Establish airway patency, hemodynamic stability, and adequate oxygenation.
If tension pneumothorax is suspected based on clinical findingsno breath sounds, hyperresonance, no tactile fremitus
on affected side, and possibly a shift in trachea away from
affected sideimmediately insert a 14-16gauge needle in
2nd intercostal space midclavicular line.
The differential diagnosis of cough is listed in Table 1 and that
for hemoptysis in Table 2. The symptoms and signs of common
causes of cough and hemoptysis are listed in Table 3.
Table 1. Differential Diagnosis of Cough

Acute (<3 weeks)
Chronic (3 weeks)
Common
Common
Postnasal drip due to common
ACE inhibitor
cold (most common), acute
Postnasal drip due to
bacterial sinusitis or rhinitis
common cold, acute
COPD exacerbation
bacterial sinusitis or rhinitis
Bronchitis
Cough-variant asthma
Less common
GERD-induced bronchitis,
Pneumonia
asthma, or laryngeal
Aspiration
inflammation
Pulmonary embolism
Postinfectious, following
Postoperative atelectasis
bronchitis
Chronic bronchitis
All causes of chronic cough
Bordetella pertussis
Less common
Eosinophilic bronchitis
Bronchiectasis
Cystic fibrosis
Interstitial lung disease
Bronchogenic carcinoma
ACE, angiotensin-converting enzyme; GERD, gastroesophageal reflux disease.
64
I SIGNS & SYMPTOMS

Evaluation of cough and/or hemoptysis should include posteroanterior and lateral chest X-rays.
Purulent sputum (thick green or yellow) suggests bronchitis,
pneumonia, bronchiectasis, or lung abscess.
A dry cough may implicate laryngeal inflammation or
habit cough.
Table 2. Differential Diagnosis of Hemoptysis

Massive (>600 mL/24 hours)
Common
Bronchiectasis
TB
Less common
Invasive aspergillosis
Mild and moderate

Common
Bronchitis, acute and chronic
Pneumonia
Less common
Lung abscess
Mitral stenosis
Pulmonary embolus
Table 3. Symptoms, Signs, and Radiographic Findings in

Common Causes of Cough and Hemoptysis
Symptoms (Sx) and signs
Sx: Nasal congestion/discharge,
feeling of drainage in throat,
underlying Sx of sinusitis or
vasomotor rhinitis
Signs: Drainage in posterior
pharynx, nasal discharge,
cobblestoning of oropharyngeal mucosa,
mucus in oropharynx
Sx: Acute onset, throat clearing,
nasal discharge, nasal obstruction, throat irritation
Sx: Sneezing, clear nasal drainage, seasonal Sx
Chest X-ray
Diagnosis
Normal
Postnasal drip
Normal
Common cold
Normal
Allergic rhinitis
65
Table 3 (continued)
Sx: Sinus pain & tenderness,
purulent nasal discharge,
tooth pain
Sx: Excessive watery discharge
associated with temperature
changes
Sx: Dyspnea, purulent sputum,
history of COPD or
smoking
Signs: Fever, hypoxemia
Sx: Cough, purulent sputum,
no history of smoking
Signs: Fever, coarse rhonchi
(may clear with cough)
Sx: Following upper respiratory
tract illness
Signs: No physical exam
findings, diagnosis of
exclusion, self-limited
Sx: Dyspnea, expiratory wheezing, prolonged expiration,
nighttime Sx
Signs: Decreased peak expiratory
flow, expiratory wheeze
Sx: Dyspnea, cough with purulent sputum
Signs: Fever, bronchial breathing,
inspiratory crackles
Sx: Dyspnea, hemoptysis, chest
pain (especially pleuritic),
risk factors*
Signs: Tachycardia, tachypnea,
pleural rub, loud P2,
right ventricle heave
Sx: Substantial smoking history,
hemoptysis, dyspnea, chest
wall pain, hoarseness
Signs: Wheezing, lymphadenopathy, Horner syndrome,
signs consistent with
pneumonitis due to
obstruction, clubbing,
hypercalcemia
Sx: Copious sputum production,
history of recurrent infections
66
Chest X-ray
Diagnosis
Normal
Acute sinusitis
Normal
Vasomotor
rhinitis
Hyperinflation
bullae, examine for
infiltrates
COPD
exacerbation
Normal
Bronchitis
Postinfectious
Normal
Hyperventilation, look for

signs of underlying
cause
Consolidation
Normal or
subtle peripheral consolidation &
atelectasis
cough
Asthma
exacerbation
Pneumonia
Pulmonary
embolism
If normal, NPV
of 100% for
bronchogenic Bronchogenic
carcinoma in
carcinoma
patients with
cough
Tram tracking Bronchiectasis

of bronchi
I SIGNS & SYMPTOMS

Table 3 (continued)
Sx: Chronic cough, night sweats,
weight loss, HIV+ or risk
factors, positive PPD, TB
risk factors
Sx: Dyspnea, orthopnea
Signs: Bilateral basal inspiratory
crackles, S3, increased
jugular venous pressure
Chest X-ray
Diagnosis
Upper lobe ab- TB

normalities,
Ghon complex
Cephalization,
Kerley B
Congestive
lines, pleural
heart failure
effusions
exacerbation
NPV, negative predictive value; P2, second pulmonic sound; S3, third heart sound.
*Risk factors: personal/family history of pulmonary embolism, deep venous
thrombosis, malignancy, postoperative immobility, oral contraceptive pills, trauma.
If TB is considered, patient must be isolated.
Small parenchymal infiltrate and enlarged hilar lymph nodes.
TEST ORDERING
Posteroanterior and lateral chest X-rays for all patients; tests
suggested according to diagnosis are listed in Table 4.
INITIAL MANAGEMENT
Disease-Specific Therapy
Angiotensin-converting enzyme (ACE) inhibitor suspected
Discontinue ACE inhibitor for 4 weeks and reevaluate
Consider angiotensin II receptor blocker
If ACE inhibitor is needed, may treat cough with cromolyn 2 puffs 4 times daily
Postnasal dripSymptomatic treatment consists of firstgeneration antihistamines and decongestants; most likely
causes and treatment include
Sinusitisantibiotics (amoxicillin, if contraindicated use
trimethoprim-sulfamethoxazole [Bactrim]), nasal steroids
Allergic rhinitisnasal steroids, second-generation antihistamines
Vasomotor rhinitisfirst-generation antihistamines, ipratropium (Atrovent)
Postinfectious coughby definition, a diagnosis of exclusion,
is self-limited
67
Table 4. Testing According to Diagnosis

Diagnosis
Acute cough (<3 weeks)
Postnasal drip
Sinusitis
Allergic rhinitis
Vasomotor rhinitis
COPD exacerbation
Bronchitis
Pneumonia
TB*
Pulmonary embolism
Chronic cough (3 weeks)
Cough-variant asthma
GERD
Suggested tests
May treat empirically, consider

sinus CT
Allergy testing
None
Arterial blood gases
Evaluate for underlying cause such
as pneumonia, pulmonary
embolus, or neoplasm
Chest X-ray, CBC, sputum Gram
stain, C/S
CBC, sputum Gram stain, blood &
sputum C/S
PPD, 3 serial sputums for AFB &
Cx, rapid PCR testing, gastric
aspirate if no sputum for AFB/Cx,
consider HIV test
D-dimer, spiral CT, V/Q scan
Methacholine challenge
Empiric trial of proton pump
inhibitors, 24-hour pH probe
AFB, acid-fast bacillus; C/S, culture and sensitivities; Cx, cultures; GERD,
gastroesophageal reflux disease; PCR, polymerase chain reaction; V/Q, ventilation-perfusion.
If symptoms are severe, may attempt therapy with ipratropium and inhaled and oral corticosteroids
TB
Isolate patient
Therapy is isoniazid (INH), rifampin, pyrazinamide, ethambutol
Regimen adjusted according to susceptibility
Consult infectious diseases if extrapulmonary TB, drugresistant, or coinfection with HIV
Bronchitis
No treatment if viral cause is suspected.
For prolonged symptoms, consider azithromycin or tetracycline.
68
I SIGNS & SYMPTOMS
Bronchiectasis
Bronchial hygiene, antibiotics directed at predominant
pathogen
If fever, antipseudomonal coverage pending sputum culture
Bordetella pertussiserythromycin
Symptomatic Therapy
Antitussive therapydextromethorphan, codeine, and ipratropium aerosol are only widely available agents
Protussive therapy
Cough associated with retained mucus secretions (e.g.,
due to bronchiectasis, cystic fibrosis, or chronic bronchitis) should not be treated with antitussive agents.
In chronic bronchitis, mucolytics have not been proved
to be effective.
HICCUP (SINGULTUS)
More than 100 causes of hiccup have been reported. The most
common are listed in Table 5.
The signs and symptoms of hiccup and the corresponding diagnosis are listed in Table 6.
TEST ORDERING
The most important diagnostic tool is a thorough history and
physical exam.
Initial recommended tests are CBC with differential, electrolytes, and chest X-ray.
Additional testing is directed by history and physical exam
findings and could include calcium, creatinine, liver function
tests, toxicology screen, and MRI or CT of head, chest, or
abdomen.
MANAGEMENT
Identify and treat the underlying cause if possible.
69
Table 5. Common Causes of Hiccup

Benign causes
Idiopathic gastric distension: aerophagia, carbonated beverages,
endoscopic insufflation
Excitement, emotion
Temperature change: hot/cold beverages, hot/cold showers, tobacco
use
Malignant causes
Anatomical: consider lesion from brainstem along course of
phrenic and vagus nerves to level of diaphragm
CNS: neoplasms, trauma, ischemia, hemorrhage
Chest: pericarditis, pneumonia, bronchitis, lung cancer
Abdomen: liver or spleen abscesses, peptic ulcer disease, gastritis,
gastric or pancreatic cancer
Medications: alcohol, anesthetics, dexamethasone, methyldopa,
sulfonamides, antiepileptics, chlordiazepoxide
Metabolic: uremia, fever, electrolyte disturbances (especially
hyponatremia)
CNS, central nervous system.
70
The following stepwise algorithm can be used for hiccups of

any cause:
Nonpharmacologic
Breath holding
Valsalva maneuver
Granulated sugar 2 g swallowed dry with little moisture
Hyperventilating into a paper bag
Direct stimulation of nasal or oral pharynx with a plastic catheter
Lifting of the uvula with tongue blade
Nasogastric tube if gastric distension is present
Pharmacologic
Chlorpromazinepatient may develop orthostatic
hypotension and bradycardia and should be monitored
Metoclopramide
Nifedipine
I SIGNS & SYMPTOMS

Table 6. Signs and Symptoms of Hiccup and
Corresponding Diagnosis
Signs and symptoms
Hiccups resolve with sleep, no
organic findings
Postoperative
Transient paralysis, dysarthria,
visual loss, headache
Seizures, fever, mental status
changes, headache
Anxiety, abdominal bloating,
abdominal pain, abdominal
gas on KUB
Diagnosis
Psychogenic or idiopathic
Anesthetics, irritation of phrenic
or vagus nerve
Stroke
Encephalitis
Aerophagia
KUB, kidney, ureter, bladder X-ray.
71
I SIGNS & SYMPTOMS

DELIRIUM AND DEMENTIA
Lionel S. Lim, M.D.
Paul Y. Takahashi, M.D.

Rule Out the Following Life-Threatening Conditions:
Hypoxia due to any cardiopulmonary process
Hypercarbia
Hypoglycemia
Intracranial process (e.g., bleeding, infarction, infection, tumor)
Infection and/or sepsis
Myocardial ischemia
Drug effect or withdrawal
Distinguish Between Delirium and Dementia by
Recognizing the Following:
Consciousness
Determine if the level of consciousness has changed.
Change of consciousness characterized by negative
symptoms such as drowsiness or lethargy or positive
symptoms such as agitation
Cognition
Alteration in mental functioning and thought processes
This alteration may be present in both delirium and
dementia.
Inattention and disorganized thinking are key features of
delirium.
Course
Deliriumcharacterized by acute changes in which the
delirium may fluctuate
Dementiamore insidious and tends to be slowly
progressive
Cause
Deliriuma consequence of an underlying medical condition or medication
73
Dementianot a consequence of an underlying medical

condition or medication
Delirium, dementia, and depression are compared in Table 1.
ADDRESSING THE RISK

Obtain the Following Information:
Temperature, pulse, blood pressure
Respiratory rateis respiratory distress or failure present?
What is the oxygen saturation? Obtain arterial blood gases.
Obtain a glucometer reading immediately.
Stabilize the Patient
Ensure the patient is hemodynamically stable. Otherwise, get
help!
Table 1. Comparison of Delirium, Dementia, and

Depression
Feature
Delirium
Onset
Course
Acute
Fluctuating
Consciousness
& orientation
Attention &
memory
Clouded, disoriented
Poor short-term
memory, inattention
Psychosis
Common (psychotic ideas are

fleeting &
simple in content)
EEG
Abnormal in
80%-90%,
generalized
diffuse slowing
in 80%
74
Dementia
Insidious
Steadily progressive
Clear until
late stages
Poor shortterm memory without
marked inattention
Less common
Abnormal in
80%-90%,
generalized
diffuse slowing in 80%
Depression
Variable
Diurnal variation
Generally
unimpaired
Poor attention
but memory
intact
Occurs in
small number
of patients
(psychotic
symptoms are
complex & in
keeping with
prevailing
mood)
Generally
normal
I SIGNS & SYMPTOMS
Maintain a patent airway; supplement breathing with oxygen.

Establish IV access, and start fluids if patient is hypotensive.
Brief History and Focused Physical Exam

Determine the patients previous and existing medical problems.
Do you suspect drug or alcohol abuse?
What are the patients current medications?
What is the patients code status?
Perform a focused neurologic, cardiopulmonary, and abdominal exam.
DELIRIUM
See Tables 2 and 3.
Table 2. Pharmacologic Causes of Delirium*

Sedatives or hypnotics (intoxication or withdrawal)
Benzodiazepines
Alprazolam
Chlordiazepoxide
Diazepam
Flurazepam
Triazolam
Barbiturates
Chloral hydrate
Ethanol
Analgesics
Opioids & opioid agonists
Meperidine (Demerol)
Methadone
Pentazocine (Talwin)
Propoxyphene (Darvon)
Antipsychotics
Low-potency, highly anticholinergic drugs
Atypical antipsychoticsclozapine
75
Table 2 (continued)
Antidepressants
Lithium
Tricyclic antidepressants
Amitriptyline
Doxepin
Imipramine
Selective serotonin reuptake inhibitors (less common)
Cardiac medications
Antiarrhythmicslidocaine
Antihypertensives
Digitalis
Gastrointestinal tract medicationshistamine (H2) blockers
Neurologic medications
Anticonvulsantsphenytoin (Dilantin)
Antiparkinsonian drugs
Antiflammatory agents
Corticosteroids
NSAIDsindomethacin (Indocin)
Antihistamines (especially first generation with sedating properties)
Diphenhydramine (Benadryl)
Other anticholinergics
Atropine
Baclofen
Benztropine mesylate (Cogentin)
Cyclobenzaprine (Flexeril)
Oxybutynin (Ditropan)
Scopolamine
*Specifically mentioned medications have a high association with delirium.

Medical History
What are the symptoms, duration of delirium, and course
(gradual or stepwise progression, rapidity of progression)?
What was previous and present functional and cognitive
status?
Any recent changes in the medical history?
Any illicit drug or alcohol use?
Any previous episodes of delirium?
In older patients, how is bowel and bladder function, i.e.,
constipation and urinary obstruction?
76
I SIGNS & SYMPTOMS

Table 3. Nonpharmacologic Causes of Delirium
Metabolic disorders
Hypoglycemia or hyperglycemia
Hypothyroidism or hyperthyroidism
Acid-base imbalance
Anemia
Vitamin deficiencies or malnutrition
Fluid & electrolyte imbalances
Hyponatremia
Hypernatremia
Hypercalcemia
Cardiovascular disorders
Cardiac arrhythmia
Shock
Hypertensive encephalopathy
Central nervous system disorders
Head trauma
Seizures
Cerebrovascular diseases
Infections
Space-occupying lesions (tumor, subdural hematoma, abscess)
Vasculitis
Pulmonary (hypoxia) disorders
Pulmonary embolism
Pneumonia
COPD
Fat embolism
Gastrointestinal disorders
Hepatic encephalopathy
Severe fecal impaction
Genitourinary disorders
Uremia
Urinary tract infection
Severe urinary retention
Infections
Sleep deprivation
Postoperative state
77
Any history of the following:

Infections (including HIV and AIDS)
Central nervous system disorder (e.g., stroke)
Hepatic or renal impairment
Recent surgical procedure
Trauma
Diabetes mellitus
Thyroid dysfunction
Chronic cardiopulmonary conditions (e.g., coronary artery
disease, congestive heart failure, COPD)
Head injury
Physical Exam
Perform a mental status exam.
Pay special attention to cardiopulmonary and abdominal
exams.
Examine the skin to assess hydration status, and check orthostatics.
Look for signs of hypo- or hyperthyroidism.
Look for focal neurologic deficits.
Delirium + Fever, Tachycardia, Tremors, Agitation,
Hypertension = Delirium Tremens (ethanol withdrawal)
Fever + Meningism = Meningitis or Subarachnoid
Hemorrhage
If patient is severely obtunded, consider diffuse encephalitis, metabolic encephalopathy, or brainstem stroke.
Metabolic encephalopathies are manifested by asterixis
(arrhythmic flapping tremor of outstretched wrists).
Special Circumstances
The elderly are at high risk for delirium because of age-related reduced physiologic reserve, underlying medical comorbidity, possible preexisting cognitive defects, polypharmacy, and
altered drug metabolism.
TEST ORDERING
Lab Tests
Routine
Chemistry panelelectrolytes (sodium, potassium,
calcium, magnesium), bicarbonate, BUN and creatinine,
glucose
78
I SIGNS & SYMPTOMS

Liver function tests
CBC
Urinalysis
Selected patients
Osmolarity
Ammonia (NH 3 ) (hepatic dysfunction and hepatic
encephalopathy)
Serum/urine toxicology (especially if comatose and/or
diagnosis is unclear)
Ethanol
Sensitive thyroid-stimulating hormone
Cultures (blood, urine, sputum)
ESR
HIV testing
TEST ORDERING
Lab Tests (to Rule Out Reversible Forms of Dementia)
Routine
CBC
ESR
Electrolytes (sodium, potassium, calcium, magnesium)
& glucose
Renal function tests (BUN, creatinine)
Vitamin B12 & folate
Syphilis serology (fluorescent treponemal antibody,
absorbed test)
Urinalysis
Thyroid screen (sensitive thyroid-stimulating hormone)
Selected patients
HIV testing
Lyme serology
Urinary heavy metals
Toxicology screen
Paraneoplastic antibodies
Antinuclear antibody
Extractable nuclear antigen
79
Neuroimaging
CT of brainpreferably performed with and without contrast
medium
MRI of brain
May be needed to identify strokes or ischemic changes
not detectable with CT
Preferably performed with and without contrast medium,
with sagittal, axial, and coronal views
Neuropsychometric Testing
Helpful in differentiating depression from dementia
In cases of false-positive or negative Mini-Mental State
Examination scores because of low educational level or high
baseline intelligence, respectively
Others (Not Routinely Used)

Genetic testing (familial forms of Alzheimer and frontotemporal dementia, parkinsonism, Creutzfeldt-Jakob disease)
Apolipoprotein E (Alzheimer dementia)
EEG (Creutzfeldt-Jakob disease, metabolic encephalopathy,
encephalitis)
ECGCardiac Ischemia or Arrhythmias

Chest X-rayCongestive Heart Failure, Pneumonia, or
Other Pulmonary Processes
Neuroimaging
CT of head with and without contrast as a screen if localized
intracranial process is suspected (e.g., hemorrhage, tumor,
infarction, subarachnoid hemorrhage, abscess)
If meningitis is suspected and papilledema, focal neurologic findings, or unconsciousness is present, it may be reasonable to perform CT of the head before performing lumbar puncture. Blood specimens must be drawn for cultures
and empiric antibiotic therapy be given while CT is pending.
In the elderly, consider performing CT of the head if there is
a history of falling, even if head injury was not reported.
CSF Exam
Perform if at least 1 of the following is suspected:
80
I SIGNS & SYMPTOMS
Meningitis
Encephalitis
Subarachnoid hemorrhage (even if CT of the head is negative); check for xanthochromia
EEG
Consider an EEG if the patient is comatose and any of the following is suspected:
Clinically unrecognized seizures
Herpes encephalitis
Creutzfeldt-Jakob disease
May be useful in diagnosing metabolic or drug-induced
delirium
INITIAL MANAGEMENT
Three components to managing delirium:
Identify and treat the underlying cause.
Use nonpharmacologic measures to ameliorate symptoms
(Table 4).
Initiate pharmacologic therapy for severe agitation and
behavioral disturbance (Table 5).
DEMENTIA
Common and other causes of dementia are listed in Table 6.
Medical History
Avoid relying solely on the patients history; obtain information from caregiver or close relative.
Localize the lesion by directing questions toward the various
domains of cognitive function (Table 7).
Neurologic syndromes associated with dementia are listed in
Table 8.
Physical Exam
Signs to look fornuchal rigidity, papilledema, focal facial
81
Table 4. Nonpharmacologic Interventions to Ameliorate

Symptoms Associated With Delirium
Environmental interventions
Optimize sensorineural input: eyeglasses, hearing aids, dentures
Overcome barriers to communication
Visual aids & alternative means of communication (e.g.,
pen & paper) for verbally impaired patient (e.g., because
of intubation, stroke)
Provide interpreter if necessary
Room modifications
Quiet environment with gentle music or television
Preserve diurnal rhythm
Lights on during day, night-lights at night
Provide a window view for day-night orientation
In-room clocks
Room near nursing station to facilitate close observation
Place familiar objects in patients room
Constant room temperature
Patient comfort measures
Adequate analgesia for pain relief while avoiding overmedication
Early mobility & physical activity
Minimize sleep interruptions
Adequate nutritional intake
Reduce unnecessary physical restraints
Psychosocial support
Maintain interaction with family & friends
Consistency in staff caring for the patient (e.g., a key nurse)
Provide regular verbal reminders to orient patient to time,
location, & people involved in patients care
82
or limb weakness or asymmetric deep tendon reflexes, parkinsonism, frontal release signs (glabellar, grasp, snout), gait
impairment, fasciculations
Parkinsonian signs may indicate either dementia with Lewy
bodies or frank Parkinson disease.
Hypertension and other cardiovascular findings and focal
neurologic signs favor diagnosis of multi-infarct dementia.
Perform a screening mental status exam such as Mini-Mental
State Examination (Table 9).
Alternatively, the clock-drawing test may be performed
ask patient to draw a clock face with the hands at 11:10.
I SIGNS & SYMPTOMS

Table 5. Pharmacologic Therapy for Severe Agitation
and Behavioral Disturbance
Haloperidol (Haldol)
0.5-10 mg IM or IV (1-2 mg PO or 0.5-1 mg IM or IV in elderly) depending on level of disturbance and likely tolerance (consider age, physical status, risk of side effects)
Observe patient for 20-30 minutes
If patient remains unmanageable but has no adverse effects,
double the dose & continue monitoring
Although occurrence of extrapyramidal side effects is low, use
caution if prescribing for patient with known Parkinson disease
Repeat the cycle until acceptable response or side effects occur
Patient should be manageable & not obtunded
Lorazepam (Ativan)
Mild to moderate agitation: 1-2 mg PO or 0.5-1 mg IM initially
Moderate to severe agitation: 1-2 mg IM or 0.5 mg IV initially
May be given every 4 hours as needed
Beneficial for reducing antipsychotic medications when
extrapyramidal side effects occur
Monitor respiratory functions & level of sedation carefully
Consider giving flumazenil if toxicity occurs
Table 6. Causes of Dementia

Common
Mild cognitive impairment
Alzheimer dementia
Dementia with Lewy bodies
Frontotemporal dementia
Vascular dementia
Normal-pressure hydrocephalus*
Other
Vitamin deficiencies
Thiamine (B1) (Wernicke encephalopathy)*
B12 (pernicious anemia) or folate deficiency*
Endocrine & other organ failure
Hypothyroidism
Adrenal insufficiency & Cushing syndrome*
Hypo- or hyperparathyroidism*
Renal failure*
Liver failure*
Pulmonary failure*
83
Table 6 (continued)
Chronic infections
HIV
Neurosyphilis*
Papovavirus (progressive multifocal leukoencephalopathy)
Prion (Creutzfeldt-Jakob disease)
TB, fungal, or protozoal*
Sarcoidosis*
Whipple disease*
Lyme disease*
Brain abscess*
Head trauma or diffuse brain damage
Chronic subdural hematoma*
Postanoxia
Postencephalitis
Neoplastic
Primary brain tumor*
Metastatic brain tumor*
Paraneoplastic limbic encephalitis
Psychiatric
Depression (pseudodementia)*
Sleep disorder
Obstructive sleep apnea*
Central sleep apnea*
Restless legs syndrome*
Periodic limb movement disorder*
Degenerative disorders
Parkinson disease
Huntington disease
Progressive supranuclear palsy
Multiple sclerosis
Toxic
Numerous (highly anticholinergic) prescription drugs*
Illicit drugs*
Heavy metals*
Miscellaneous
Vasculitis*
Acute intermittent porphyria*
Recurrent nonconvulsive seizures*
*Potentially treatable dementia.
84
I SIGNS & SYMPTOMS

Table 7. Localization of Cognitive Domain
Cognitive domain
Location
Does patient...
Memory
Mesial temporal lobe Recall the details of

recent events?
Tend to repeat
questions?
Executive functions Frontal lobe
Demonstrate poor
judgment?
Have difficulty planning & reasoning?
Behave in inappropriate, overly joyful,
overly tearful, or
markedly sedentary
manner?
Language
Dominant hemisphere Struggle to recall
(usually left) in
names of persons or
frontotemporoparietal objects?
area
Struggle to express
his/her thoughts?
Struggle to understand oral or
written information?
Calculations
Dominant hemisphere Balance the check(usually left) in
book without errors?
parietal area
Struggle to make
Can be impaired when correct change?
attention poor, e.g.,
frontal lobe dysfunction
Limb praxis
Dominant hemisphere Operate a car with
(usually left) in
difficulty?
parietal or mesial
Use eating utensils or
frontal area
tools correctly?
Dressing praxis
Nondominant hemis- Have trouble getting
phere (usually right) dressed?
in parietal area
Visuospatial function Nondominant hemis- Get lost in the home,
phere (usually right) in stores, or while
in parietal area
driving?
85
Table 8. Neurologic Syndromes Associated With

Dementia*
Associated syndrome
Impairment in memory only
Impairment in memory &
other cognitive domain(s)
Visual hallucinations, parkinsonism, visuospatial abnormalities
Acting out dreams
Restless legs
Leg twitching
Episodes of frequent arousals
& gasping for air
Personality/behavioral change
and/or language disturbance
Stroke + stepwise cognitive
decline
Cognitive decline, ataxic gait,
urinary incontinence
Likely diagnosis
Mild cognitive impairment
Alzheimer dementia
REM sleep behavior disorder

Restless legs syndrome
Periodic limb movement disorder
Obstructive sleep apnea
Vascular dementia
Normal-pressure hydrocephalus
*All prescription and nonprescription drugs should be scrutinized for potential cognitive side effects.
Alcohol intake and nutrition screening for possible thiamine deficiency.
(Score5, perfect; 4, minor visuospatial error; 3, 10 inaccurately placed; 2, moderate disorganization of numbers; 1,
fails to draw a basic representation of a clock)
Physical exam and history clues to the diagnosis are given in
Table 10.
INITIAL MANAGEMENT
Basic Principles
Treat any correctable cause of dementia.
Ensure that infections, hypoxia, dehydration, metabolic disturbances, pain, and constipation are treated effectively.
Correct hearing or visual loss to extent possible.
Avoid agents with anticholinergic properties.
Minimize psychoactive medications with possible adverse
cognitive side effects to the fewest agents at the lowest effective doses.
Nonpharmacologic intervensions (see Table 4)
86
I SIGNS & SYMPTOMS

Table 9. Mini-Mental State Examination
Points
1. Orientation
Name: season, date, day, month, year
Name: hospital, floor, town, state,
country
2. Registration
Identify 3 objects by name and ask
patient to repeat
3. Attention and calculation
Serial 7ssubtract from 100 (e.g.,
93, 86, 79, 72, 65)
4. Recall
Recall the 3 objects presented earlier
5. Language
Name pencil & watch
Repeat No ifs, ands, or buts
Follow a 3-step command (e.g., Take
this paper, fold it in half, and place it
on the table)
Write close your eyes, and ask patient
to obey written command
Ask patient to write a sentence
Ask patient to copy a design (e.g., intersecting pentagons)
Total
5 (1 for each name)

5 (1 for each name)
3 (1 for each object)
5 (1 for each subtraction)

1
3 (1 for each command)
1
1
1
30*
*Score <24 is abnormal.
Pharmacologic Therapy
Alzheimer dementia
Vitamin E 1,000 IU twice daily
Donepezil (Aricept), galantamine (Reminyl), rivastigmine
(Exelon), or tacrine (Cognexthis is rarely used because
of side effects, especially hepatotoxicity)
Donepezil or rivastigmine for behavioral symptoms
Use carbidopa-levodopa (Sinemet) for cognitive or motor
symptoms; avoid if psychosis is present.
87
Table 10. Physical Exam and History Clues to the

Diagnosis
Presentation
Atypical course
Rapidly progressive
Waxing and waning
Series of abrupt changes in
clinical course
Systemic symptoms
Headache
Fever
Dry eyes/mouth
Myalgias
Arthralgias
Weight loss
Skin lesions
Sleep disorder
Excessive daytime somnolence
Loud snoring
Observed apnea
Motor restlessness/insomnia
Leg jerks while sleeping
Neuropsychiatric symptoms
Behavioral/personality change
Apathy
Visual hallucinations
Delusions
Agitation
Neurologic symptoms or signs
Diplopia
Dysphagia
Face or limb weakness or
numbness
Gait unsteadiness
Parkinsonian signs
Masked facies
Abnormal gait
Stooped posture
Tremor
Rigidity
88
Possible causes
Vascular, infectious, toxic/
metabolic processes, vasculitis, multiple sclerosis,
dementia with Lewy bodies,
frontotemporal dementia,
vascular dementia, Creutzfeldt-Jakob disease
Infection, vasculitis, neoplastic,
paraneoplastic processes
Obstructive sleep apnea,

central sleep apnea, restless
legs syndrome, periodic limb
movement disorder
Dementia with Lewy bodies,

frontotemporal dementia,
infection, vasculitis,
toxic/metabolic processes
Brain tumor, abscess
Parkinson disease, dementia

with Lewy bodies, normalpressure hydrocephalus
I SIGNS & SYMPTOMS

Avoid conventional neuroleptic agents because parkinsonism can worsen.
Delusions, hallucinations, agitation may respond to selective serotonin reuptake inhibitors, carbamazepine, valproic acid, or newer neuroleptic agents (e.g., quetiapine).
Treat underlying depression.
Donepezil, rivastigmine, carbidopa-levodopa, and psychostimulants can help cognitive symptoms.
Behavioral dyscontrol may respond to selective serotonin
reuptake inhibitors, carbamazepine, or valproic acid.
Vascular dementia
Control hypertension and diabetes.
Aspirin, clopidogrel (warfarin for selected causes)
Normal-pressure hydrocephalus
Consider ventriculoperitoneal shunt, especially if symptoms have been present <2 years.
Carbidopa-levodopa may be helpful in some patients.
Nonpharmacologic Therapy
Promote establishment of a daily routine.
Regular light exercise
Support groups (Alzheimer Association)
Address safety issues.
Driving assessment
Home environment
Wandering
89
I SIGNS & SYMPTOMS

DIARRHEA
DEFINITION
Stool weight >250 g/day
ACUTE DIARRHEA
Is the Patients Life at Risk?
Risk can be from underlying disease process or secondary
effects.
Potentially Dangerous Diseases
Invasive infection: Salmonella, Shigella, other
Toxin: hemolytic uremic syndrome from Escherichia coli
O157:H7
Ischemia: ischemic bowel
Poisoning: organophosphate exposure
Gastrointestinal bleed (is this really melena?)
Impaction, early obstruction, toxic megacolon
Secondary Effects
Hypovolemia: dehydration
Electrolyte abnormalities: sodium, potassium, bicarbonate
Anemia (if blood loss)
Immediate Evaluation
History
Frequency and volume of stool, e.g., large volumedehydration?
Special abbreviations used in this chapter: EGD, esophagogastroduodenoscopy;

O&P, ova and parasites; SBFT, small-bowel follow-through; VIP, vasoactive
intestinal peptide.
91
Character of stool, e.g., black tarmelena?

Abdominal pain: severe pain in ischemia, cramping relieved
with defecation in infection, dull ache with impaction
Past history: abdominal surgery, HIV-positive
Recent hospitalization or antibiotic use (Clostridium difficile?)
Medications
Examination
Vital signs: fever >38.3C, hypotension, tachycardia,
orthostasis
Dehydration (physical exam is unreliable in adultsin evaluation, consider skin turgor, orthostasis, flat jugular venous
pressure, tachycardia, hypotension)
Abdomen: peritoneal signs
Rectal: frank blood or melena indicates gastrointestinal bleed;
occult or streaked blood suggests inflammatory diarrhea.
Further Evaluation Directed by History and Exam Findings

CBC, electrolytes, and renal function
Consider abdominal X-ray.
Consider fecal WBCs, Clostridium difficile toxin, and bacterial
culture. Blood culture if severely ill or known HIV-positive
Addressing the Risk

Is There Hypovolemia/Dehydration?
IV access
Normal saline
Record volume input and output.
Type and screen for transfusion if possible bleeding.
Assess electrolytes and renal function.
Is There Severe Abdominal Pain?
Consider surgical consult
Check liver chemistry values (ALT, alkaline phosphatase,
bilirubin), amylase, serum lactate.
NPO
IV fluids
Abdominal X-ray; consider abdominal CT.
Is There Question of Severe Infection?

Consider antibiotics after obtaining stool cultures.
92
I SIGNS & SYMPTOMS

Infectious
Acute diarrhea is nearly always infectious in outpatients,
less so in inpatients.
Invasive bacteria: Campylobacter jejuni, some E. coli,
Salmonella spp., Shigella spp., Yersinia enterocolitica
Toxigenic bacteria: Clostridium difficile, Vibrio cholerae,
some E. coli
Parasitic: amebae, Giardia, Cryptosporidium, Cyclospora
Virus: adenovirus, Rotavirus, Norwalk virus
Food poisoning: Bacillus cereus, Clostridium perfringens,
Staphylococcus aureus, other Vibrio spp., Listeria monocytogenes
Medications
Antibiotics, antacids (magnesium), laxatives, quinine, digoxin, NSAIDs, sorbitol, colchicine, tube feedings, herbal remedies
Toxins
Organophosphates
Diet
Undigested sugars (lactose in milk, sweeteners like sorbitol,
fructose from fruit or juice), fiber
Ischemia
Impaction
Key DistinctionInflammatory vs. Noninflammatory
Inflammatory
Usually arises from the colon = low volume, may be mucoid
Dysentery = abdominal pain/cramp, fever, WBCs and
RBCs in stool
Noninflammatory
Usually from the small bowel = large volume, watery
No WBCs or RBCs in stool
The history provides the majority of information.
93
Onset, Duration
More than 3 weeks is chronic
Frequency, Volume, and Form of Stool; Nighttime Stool;
Incontinence
Is this true diarrhea (>250 mL) or simply loose stool or frequent defecation?
Absence of nighttime stool suggests condition is not
organic.
Incontinence may imply an anatomic (or neurologic)
abnormality.
Blood, Pus, Mucus, Oil/Grease
Mucus suggests irritable bowel syndrome or infection.
Oil (steatorrhea) suggests fat malabsorption (see Chronic).
Pain, Fever, Weight Loss

Pain more impressive than exam suggests ischemia.
Rectal pain and urgency = tenesmus, suggests inflammation.
Fever suggests inflammation.
Recent Travel, Camping, Swimming, Eating

Trip to Mexico, for example, suggests travelers diarrhea
or parasite.
Camping suggests Giardia infection.
Eating history may suggest food poisoning.
Diet
Dairy: lactose intolerance is common.
Sorbitol (included in many diet foods) and fructose (fruits,
juices) can cause diarrhea.
Ethanol in excess
Medications
New medications, laxatives, antibiotics; self-treatment for
constipation
Abdominal Operations, HIV Status, Other Medical

Conditions
Previous surgery may suggest partial obstruction.
AIDS has its own differential (not discussed here).
94
I SIGNS & SYMPTOMS

Test Ordering
Usually not necessary in acute diarrhea in an outpatient
setting without dysentery
Further Evaluation Is Indicated If
Significant pain
Fever (>38.3C)
Dehydration
Bloody stool
Extended duration (>5 days)
Further Evaluation Includes

Stool WBC, ova and parasites (O&P), Clostridium difficile
toxin; consider bacterial culture
Cultures are rarely positive (<10%) unless WBCs are present (then 75% positive) or other red flags are present.
Stool cultures or O&P for new diarrhea after 3 days of hospitalization is virtually useless (but check C. difficile toxin).
When checking O&P or C. difficile toxin, 3 negative tests
are required to reliably rule out infection.
CBC, electrolytes, creatinine/BUN
Consider abdominal X-ray.
Consider flexible sigmoidoscopy.
Management
Nearly all acute diarrhea is mild, self-limited, and resolves
in <5 days.
Hydration (PO preferred with balanced rehydration solution; IV if needed)
Specific treatment if cause is known
Bismuth subsalicylate (Pepto-Bismol)
Antidiarrheal (If Not Inflammatory)

Loperamide (Imodium)
Diphenoxylate with atropine (Lomotil)
Antibiotics
Often not indicated
95
Treat (only if not improving spontaneously)

Antibiotic resistance is often a problem and varies geographically.
Shigella (ampicillin), Vibrio parahaemolyticus (erythromycin), Yersinia enterocolitica (trimethoprim-sulfamethoxazole [Bactrim]), Campylobacter jejuni
(ciprofloxacin), V. vulnificus (tetracycline)
Fluoroquinolones are also effective.
Do not treat Salmonella (except if severe or systemic, then
with ciprofloxacin) because it may prolong carriage state.
Do not treat E. coli O157:H7 because it may increase the
risk of hemolytic uremic syndrome.
CHRONIC DIARRHEA (>3 WEEKS)

Osmotic
Medications including laxatives
Undigested sugars
Carbohydrate malabsorption: sorbitol, lactulose, mannitol, fiber
Enzyme dysfunction: lactose, fructose
Fatty (Subset of Osmotic)
Maldigestion
Decreased bile salts: cirrhosis, bile duct obstruction, ileal
resection
Pancreatic dysfunction: chronic pancreatitis, cystic fibrosis,
duct obstruction
Malabsorption
Celiac sprue, tropical sprue
Short-bowel syndrome
Bacterial overgrowth: diabetes mellitus, scleroderma,
previous bowel surgery
Lymphatic obstruction
Infection: Giardia, Isospora, Mycobacterium aviumintracellulare, Tropheryma whippelii (Whipple disease)
Secretory
Endocrine
Gastrointestinal: vasoactive intestinal peptide (VIP)secreting tumor (VIPoma), carcinoid tumor, gastrinoma,
medullary thyroid cancer
96
I SIGNS & SYMPTOMS

Systemic: Addison disease, hyperthyroidism
Stimulant laxatives, other medications
Villous adenoma, lymphoma
Connective tissue diseases: vasculitis, systemic lupus
erythematosus, mixed connective tissue disease
Bile salt malabsorption (ileal resection)
Inflammatory
Inflammatory bowel disease: ulcerative colitis, Crohn disease,
lymphocytic or collagenous colitis
Malignancy: colon cancer, lymphoma
Radiation colitis or enteritis
Infection (see below)
Ischemia
Motility
Postsurgical: vagotomy, sympathectomy
Scleroderma
Diabetes mellitus
Hyperthyroidism
Irritable bowel syndrome
Infection
Parasite: Giardia, ameba
HIV-related: Cyclospora, Microsporida, Cryptosporidium,
Isospora, Mycobacterium avium-intracellulare complex
TB
Clostridium difficile
Viral: cytomegalovirus, herpes simplex virususually
immunocompromised host

History
Same as for acute diarrhea
Examination
Same as for acute diarrhea, plus signs of systemic illness
Skin: flushing (serotonin syndrome), rash, erythema nodosum
97
Oral: inflammatory bowel disease, celiac sprue

Ocular: inflammatory bowel disease, Reiter syndrome
Joints: inflammatory bowel disease, Whipple disease, connective tissue disease
Lymphadenopathy
Test Ordering
Stage IClassify Diarrhea
Stool: WBCs, Clostridium difficile toxin, occult blood, pH,
electrolytes (sodium, potassium, osmolality), 72-hour fecal
fat (on a high fat diet), laxative screen (magnesium, sulfate
[SO4], phosphate [PO4])
WBCs or RBCs = inflammatory
Low pH = sugar malabsorption
Osmolar gap = 290 [(sodium + potassium) 2]
Gap <50, sodium >90 = secretory
Gap >100, sodium <60 = osmotic
If possibility of dilution (urine, water), check osmolality.
>375 = urine (sodium usually >150)
<200 = water
>14 g fat/24 hours = steatorrhea (malabsorptive)
7-14 g indeterminate
Blood: CBC, ESR, electrolytes, albumin, INR, thyroidstimulating hormone
Anemia: consider inflammatory bowel disease, malabsorption, malignancy.
Eosinophils:
consider parasite (Strongyloides),
eosinophilic enteritis, malignancy.
High ESR: consider inflammatory bowel disease, malignancy, connective tissue disease.
Low sodium, high potassium: consider Addison disease.
Low albumin, high INR: consider malabsorption.
Note: If long-standing diarrhea, consider nutrition evaluation (25-OH vitamin D, zinc, iron, vitamin B12, folate
in addition to INR and albumin).
Stage IIEvaluate According to Class
Secretory diarrhea
Increased secretion of electrolytes, normal osmolar gap
Large volume, no change with fast
Infection?: bacterial culture, O&P 3, Giardia antigen, HIV
98
I SIGNS & SYMPTOMS
If HIV-positive, must check (in addition to above) for

Cyclospora (modified acid-fast stain), Cryptosporidium
(ELISA preferred to modified acid fast), and
Microsporida
Structural defect?: small-bowel follow-through (SBFT),
colonoscopy, abdominal CT, upper endoscopy esophagogastroduodenoscopy (EGD) with small-bowel biopsy
Endocrine?: serum gastrin, VIP, calcitonin, somatostatin;
urine 5-hydroxyindoleacetic acid, metanephrine/catecholamines, histamine; consider adrenocorticotropic
hormone stimulation test
Bile acid malabsorption?: consider trial of cholestyramine
Consider serum protein electrophoresis
Osmotic diarrhea
Improves with fasting
Increased osmolar gap
Low pH (<6)
Undigested sugars?: review diet and medications (sorbitol)
Hydrogen breath (H2) test
High stool magnesium, SO4, PO4: laxative or antacid use
Fatty (subset of osmotic) diarrhea
Weight loss, nutrition deficiency, steatorrhea
Small-bowel disorder?: SBFT, EGD with small-bowel
biopsy (including Congo red stain for amyloid)
Pancreatic insufficiency?: secretin stimulation test, cholecystokinin stimulation test, stool chymotrypsin activity,
abdominal CT
Bacterial overgrowth?: small-bowel quantitative culture
(or empiric trial of antibiotics)
Inflammatory diarrhea
SBFT, colonoscopy, abdominal CT
Infection?: stool bacterial culture, O&P 3, Clostridium
difficile toxin 3; serum HIV screen
Management
General Measures
Hydration if needed
If specific cause is found, treat it (below).
99
Otherwise
Try dietary changes: cut out dairy, caffeine, diet foods
(sorbitol), fruit (fructose), ethanol.
Treat symptoms: if noninflammatory, loperamide or diphenoxylate with atropine (Lomotil) can be used, as under
Acute.
Irritable Bowel Syndrome (Diarrhea-Predominant)

May not meet strict definition for diarrhea (frequent bowel
movements, but usually normal stool volume)
Definition: chronic, recurrent abdominal pain with altered
bowel movements; characterized further by the Rome
criteria
Treatment
Education
Food, dairy: triggers?
Fiber helps in some cases
Loperamide or diphenoxylate with atropine
Treat pain
Daily cramps: tricyclic antidepressant or selective
serotonin-reuptake inhibitor
Occasional cramps: as needed, antispasmodic
dicyclomine, hyoscyamine (Levsin)
Laxative Use/Abuse or Carbohydrate Malabsorption

Stop laxative or modify diet as needed.
Lactase deficiency: lactase supplement (Lactaid)
Bile Salt Malabsorption

Try cholestyramine.
May paradoxically worsen diarrhea (if it leads to bile salt
deficiency)
If so
Stop cholestyramine.
Diet modification: low fat (<50 g/day), may need supplementation with medium-chain triglycerides
Pancreatic Insufficiency
Pancreatic enzyme supplementation (various formulations)
Nonencapsulated formulationsmay be inactivated in
acidic stomach, consider adding proton pump inhibitor.
100
I SIGNS & SYMPTOMS
Encapsulated formulations are protected from acid, but

capsule may not dissolve in the duodenum.
Bacterial Overgrowth
Amoxicillin-clavulanate (Augmentin), ciprofloxacin, or
metronidazole: 1- to 2-week course
If symptoms improve and recur, treat again.
May need long-term rotating antibiotics
Celiac Sprue
A response to a gluten-free diet is part of the diagnosis as well
as the only available treatment.
Lack of effect of diet or recurrent symptoms in a previously
compliant patient, consider
Noncompliance
Alternate diagnosissmall-bowel lymphoma, refractory
sprue, microscopic colitis
Inflammatory Bowel Disease

See chapter on Inflammatory Bowel Disease
101
I SIGNS & SYMPTOMS

DIZZINESS AND VERTIGO
Yoon-Hee K. Cha, M.D.
Scott D. Eggers, M.D.
David A. Froehling, M.D.
Dizziness or vertigo can be the presenting symptom of vertebrobasilar ischemia or hemorrhage, particularly in older
patients with thromboembolic risk factors (e.g., hypertension, diabetes mellitus, arrhythmia, valvular disease) or a
bleeding diathesis.
Most serious cerebrovascular lesions causing vertigo, such as
infarction or hemorrhage of the brainstem or cerebellum, are
associated with focal neurologic deficits, including extremity
and gait ataxia, dysarthria, diplopia, facial pain or weakness,
Horner syndrome, sensory changes, or unilateral weakness.
Transient ischemic attacks generally resolve in minutes,
before the physician has seen the patient, so the history and
context are critical to making the diagnosis.
ADDRESSING THE RISK
The most important step in the evaluation of patients with
dizziness is to clarify the nature and temporal course of the
symptoms with a detailed history.
Are symptoms precipitated by head movement?
Are there focal neurologic deficits?
What are associated symptoms (e.g., palpitations, headache,
paresthesias, tinnitus, hearing loss, angina, nausea,
vomiting)?
Has there been head trauma or exposure to ototoxic
medications?
What are the patients other medical problems (e.g.,
diabetes mellitus, cardiac disease, psychiatric problems)?
Special abbreviation used in this chapter: BPPV, benign paroxysmal positional

vertigo.
103
Dizziness is classified in Table 1.
Features of peripheral and central vertigo are compared in
Table 2.

Bedside ExamDetermine Whether Symptoms Arise
From the Vestibular System or Elsewhere
Baseline
Vital signsincluding orthostatic blood pressure
Cardiac examcarotid bruits, arrhythmia, aortic stenosis
Table 1. Classification of Dizziness

Vertigothe illusion of movement (spinning, rocking, tumbling)
Recurrent positional vertigo
Benign paroxysmal positional vertigo
Craniocervical junction abnormalities (uncommon)
Brain neoplasms (rare)
Recurrent spontaneous episodes of vertigo
Vertebrobasilar transient ischemic attacks
Meniere syndrome
Vestibular migraine
Autoimmune/syphilitic
Prolonged spontaneous episode of vertigo
Vestibular neuritis
Infarction or hemorrhage of labyrinth, brainstem, or
cerebellum
Multiple sclerosis
Dysequilibriuma loss of balance or equilibrium
Visual disturbance, peripheral neuropathy, ataxia, extrapyramidal syndrome, Wernickes encephalopathy
Presyncopethe feeling of impending loss of consciousness
Orthostatic hypotension, myocardial infarction, vasovagal
reaction, cardiac arrhythmia, vascular disease
Psychogenic
Anxiety, depression, panic attack, hyperventilation, hypochondriasis
104
I SIGNS & SYMPTOMS

Table 2. Comparison of Peripheral and Central Causes of
Vertigo
Feature
Symptoms/signs
Nausea/vomiting
Imbalance
Hearing loss
Neurologic symptoms
Romberg sign
Nystagmus
Peripheral
Severe
Mild (fall to side
of lesion)
May occur
Rare
Present
Horizontal
torsional
Same direction
in all gaze
positions
Central
Variable
Severe (unable to
stand)
Rare
Common
Variable
Vertical or
torsional
Direction changes
with gaze
position
Neurologic examfocal deficits, especially cranial nerve

abnormalities or ataxia
Medication listaminoglycosides, anticonvulsants, antihypertensives, diuretics, tranquilizers
If age >45 years, order ECG and glucose.
Consider giving thiamine if Wernicke encephalopathy is a
possibility
Neuro-otologic Testing
Nystagmus
Centralclues to central causes of nystagmus include pure
vertical, torsional or direction-changing nystagmus, lack of
fatigability, or lack of suppression with visual fixation.
Note effect with convergence (e.g., downbeat converting
to upbeat in Wernicke encephalopathy). Other neurologic signs/symptoms suggest central cause.
Peripheral
Nystagmus occurs in one direction regardless of eye position and is often suppressible by visual fixation.
Note direction of the nystagmus (named by the fast phase)
and effect of eye position on nystagmus.
105
Peripheral lesions usually produce mixed horizontal/torsional (vestibular neuritis) or vertical/torsional (benign
paroxysmal positional vertigo [BPPV]) nystagmus.
Head Thrust (Head Impulse) Testing

A simple, effective bedside test to determine peripheral
vestibular hypofunction but requires practice to interpret
(see Arch Neurol. 1988;45:737-9).
Occlusive Ophthalmoscopy
Observe for movement (spontaneous nystagmus) of the optic
disk with the patient visually fixating on a distant target with
the other eye.
Then cover the other eye with your hand and observe whether
nystagmus develops or intensifies.
Nystagmus enhanced by removing visual fixation is generally of peripheral origin.
Positional TestingDix-Hallpike Maneuver

With the head turned 45 to the side, the patient is rapidly
taken from a sitting to supine position, with the head hanging 30 over the table (Fig. 1). The test is repeated for each
side.
A positive test for BPPV includes a 3-10second latency,
followed by a mixed upbeat/torsional nystagmus, with the top
pole of the eye beating toward the affected (lower) ear. This
usually reproduces the patients vertigo.
30
45
Fig. 1. Dix-Hallpike maneuver.

106
I SIGNS & SYMPTOMS
Nystagmus usually lasts <30 seconds and fatigues with

repeated testing.
Dynamic Visual Acuity

Patient reads letters on handheld Snellen chart as the examiner
rocks patients head horizontally or vertically twice per second.
Loss of more than 1 line of visual acuity suggests bilateral
vestibular hypofunction.
Vestibulospinal Reflexes
Romberg signelicited by having patient stand with feet
together and then closing eyes
If either proprioceptive or vestibular reflexes are diminished, patient loses balance.
If problem is vestibular, patient tends to fall to side of lesion.
Tandem gaitassessed by having patient walk forward and
backward heel to toe
INITIAL MANAGEMENT
Suspected Cerebral Infarction or Hemorrhage
Emergent non-contrast head CT
Stroke work-up and treatment (tissue plasminogen activator?) as indicated
Caveat: large cerebellar infarction or hemorrhage may produce life-threatening edema and brainstem compression
requiring neurosurgical decompression
Benign Paroxysmal Positional Vertigo
The most common cause of vertigo; more frequent with
advancing age
Characterized by vertigo and nystagmus associated with
changes in head position
Vertigo generally lasts <1 minute, frequent episodes
Causedislocation of calcium carbonate crystals from
labyrinthine utricle into posterior semicircular canal
Diagnosisbased on history and appearance of latent,
fatigable, torsional/vertical nystagmus on Dix-Hallpike
maneuver
107
Treatmentcanalith repositioning (Epley) maneuver, which

attempts to liberate the crystals from posterior semicircular
canal (see N Engl J Med. 1999;341:1590-6).
Vestibular Neuritis (Also Called Vestibular Neuronitis,

Acute Labyrinthitis)
Second most common cause of vertigo
Spontaneous vertigo and nausea lasting days and gradually
recovering
Diagnosisspontaneous unidirectional horizontal/torsional nystagmus from the acute peripheral unilateral vestibular
hypofunction (fast phases away from the affected ear).
Absence of other signs/symptoms, caloric testing
If hearing loss, fever, recent otitis media, rule out bacterial
labyrinthitis
Head CT or MRI with gadolinium if any suspicion of central
cause
Treatmentoral prednisone 100 mg daily with 3-week taper
improves recovery if started within 2 days after disease onset.
Vestibular suppressants (meclizine, promethazine) for 2472 hours as needed, early vestibular rehabilitation
108
I SIGNS & SYMPTOMS

DYSPNEA
Lin Y. Chen, M.D.
Is problem acute, chronic, or acute on chronic?
If acute or acute on chronic, what is the severity?
Indications of increased severity
Altered mental status
Hemodynamic instability
Oxyhemoglobin saturation <88%
Altered respiratory pattern
Inability to speak normally in full sentences
Posturesitting up and hunching forward
Rapid and shallow breathing
Accessory muscle use with supraclavicular retractions
Thoracoabdominal dyssynchrony (signals impending
respiratory failure)
Stridor (signals upper airway obstruction)
Always consider the following life-threatening conditions:
Pulmonarytension pneumothorax, asthma/COPD exacerbation, pneumonia, pulmonary embolism
Cardiacacute myocardial infarction, congestive heart
failure, cardiac tamponade, valvular disease
ADDRESSING THE RISK
Determine patients cardiopulmonary history.
Establish the following fundamental factors:
Patent airwayexclude upper airway obstruction (in sedated patient, tilt head back and lift mandible while standing at head of bed).
Hemodynamic stability
Special abbreviations used in this chapter: ABG, arterial blood gas; FIO2, fraction
of inspired oxygen.
109
Adequate oxygenation
Target PaO2 >60 mm Hg and/or oxygen saturation >90%
(Table 1)
Call Respiratory Therapy for assistance.
If hypercarbia is not a concern, start with high FIO2 and
titrate oxygen flow by pulse oximeter or arterial blood
gas (ABG) results.
If hypercarbia is a concern, slower oxygen titration with
serial ABGs is required.
To ICU for high flow oxygen delivery or assisted ventilation (invasive or noninvasive) if satisfactory oxygenation, mental status, and acid-base status (pH 7.30)
not achieved
The differential diagnosis of acute dyspnea is broad and can
be organized as shown in Table 2.
Constellation of certain history, physical exam, and lab data
suggest the diagnosis, as shown in Table 3.
The order and urgency of tests depends on patients status
(Table 4). All patients should have a pulse oximeter check and
most need ABGs, chest X-ray, ECG, and CBC.
INITIAL MANAGEMENT
Asthma Exacerbation
Oxygen to correct hypoxemia, goal is saturation >90%
Nebulized albuterol (0.5 mL of 0.5% solution [2.5 mg] in
1.25 mL normal saline) ipratropium bromide (2.5 mL of
0.02% solution [0.5 mg])
Frequency depends on severity of symptoms and medication side effects.
Rangecontinuous to every 20-60 minutes to every 2-6
hours
Titrate frequency to patients exam and peak flows.
Methylprednisolone (60-80 mg IV every 6-8 hours)
Identify and treat precipitating cause(s); consider antibiotics
if purulent sputum.
110
Table 1. Low Flow Methods for Administration of Acute Oxygen Therapy

Oxygen delivery device
Indications
Nasal canula (also applies to Less hypoxic patients

nasal masks such as nasal
scoop or nasal cup)
Venturi mask
FIO2
0.25-6 L/min
0.24-0.40, depends
on patients minute
ventilation
Simple to use
Free access to
mouth
0.24, 0.26, 0.28, 0.30,

0.35, 0.40, 0.50
Precise FIO2
Controlled oxygen ther- Flow rate varies

apy (e.g., acute-onwith FIO2
chronic hypercapnic
setting
respiratory failure
from COPD)
FIO2 needs >0.40
5-10 L/min
Partial rebreather mask (no Severely hypoxic

valves in mask, first 1/3 of patients
expired air enters reservoir
bag & is rebreathed)
111
Non-rebreather mask (1-way Severely hypoxic

valves on mask direct
patients
exhaled air out of mask,
not into reservoir bag)
10-15 L/min
(enough to keep
reservoir bag
2/3 full during
inspiration)
10-15 L/min
(same as for
partial rebreather mask)
Advantages
Disadvantages
Imprecise, limited
FIO2
Difficult to exceed
flow rates >6 L/min
Maximum FIO2 50%
0.30-0.60, depends on Useful in patients Mask may be difpatients minute venwith moderate
ficult to tolerate
tilation & mask fit
oxygen require(tight-fitting mask
ments
essential)
0.50-0.80
Useful in patients Mask may be difwith high oxyficult to tolerate
gen requirements
0.60-0.90
Useful in patients Mask may be difwith high oxygen ficult to tolerate

requirements
I SIGNS & SYMPTOMS
Simple face mask
Oxygen
Beware: history of intubation during exacerbations, elderly patient, pregnant, significant comorbidities, history of
steroid-induced problems
Follow with exams and peak expiratory flows at least twice
daily.
To ICU if PCO2 >40 with severe airflow obstruction, no
improvement or deterioration in speech, mental status, vital
signs despite therapy
Table 2. Causes of Acute Dyspnea

Pulmonary
Asthma exacerbation
COPD exacerbation
Pneumonia
Pulmonary embolism
Upper airway obstruction (trauma, neoplasm, epiglottitis,
laryngeal edema, foreign body)
Pleural disease
Interstitial lung disease
Neoplasm
Atelectasis
Cardiac
Acute myocardial infarction
Cardiac tamponade
Arrhythmias
Valvular disease
Cardiomyopathy
Neuromuscular
Myopathy
Myasthenia gravis
Spinal cord disorder
Guillain-Barr syndrome
Others
Anemia
Hyperthyroidism
Acidosis
Sepsis
Shock
Pain
Intra-abdominal process
Anxiety
112
Table 3. Diagnosis of Cause of Dyspnea

History
Acute dyspnea, chest pain,
cough
Obstructive lung disease
More gradual-onset dyspnea,

orthopnea, paroxysmal
nocturnal dyspnea
Trachea deviates away from hyperresonant

lung field with breath sounds
Wheezing, prolonged expiration, accessory
respiratory muscle use, peak expiratory
flow rate, pulsus paradoxus ( systolic
blood pressure >10 mm Hg in inspiration
vs. expiration)
Fever, bronchial breath sounds, crackles
Chest X-ray
Visceral plural line visible
Pneumothorax
Hyperinflated lung fields
Asthma/COPD
exacerbation
Infiltrates, effusion
Pneumonia
113
Nonspecific ( hemidiaphragm,
atelectasis, parenchymal
densities, unilateral effusion)
or blood pressure & heart rate, crackles, May be normal, signs of
murmurs, ST-segment changes on ECG,
congestive heart failure
CK, CK-MB, troponin
Kerley B lines, pleural effusion, periBibasilar crackles, 3rd heart sound,
jugular venous pressure
hilar congestion, engorged upper
lung zone vessels, cardiomegaly,
interstitial or alveolar infiltrates
Ptosis, dysphagia, fatigability, proximal
-weakness
Ascending weakness, areflexia
-Tachypnea, crackles, tachycardia
Diagnosis
Pulmonary embolism
Acute myocardial
infarction
Congestive heart
failure
Myasthenia gravis
I SIGNS & SYMPTOMS
Cough, phlegm production,

pleuritic chest pain
Acute dyspnea, pleuritic
chest pain, risk factors for
venous thromboembolism
Chest pain/pressure
Exam
COPD Exacerbation
Oxygen to correct hypoxemia, administer carefully if hypercapnia is a concern
Nebulized bronchodilators
Methylprednisolone (60-125 mg IV every 6-8 hours)
Identify and treat precipitating cause(s); give antibiotics if new
onset of sputum production or change in sputum quality.
Table 4. Tests According to Signs, Symptoms, and Diagnosis
Symptoms/signs
Diagnosis
Wheezing, prolonged COPD or asthma

expiration
exacerbation
Fever, productive
cough, bronchial
breath sounds or
crackles
Pneumonia
Pleuritic chest pain,

hemoptysis, right
parasternal heave,
loud P2, jugular
venous distension,
tachycardia
Chest pain radiating
to arm & jaw, diaphoresis, nausea
Orthopnea, PND,
jugular venous distension, displaced
PMI, 3rd heart
sound
Pulmonary embolism
Tests ordered
CXR, ABG, pre-/postbronchodilator peak
expiratory flow
CXR; ABG; sputum
Gram stain/culture;
blood cultures (2);
CBC with differential,
chemistry panel;
thoracocentesis with
stains/cultures & pH,
LDH, protein, glucose
CXR, ABG, ECG,
D-dimer, CT angiography vs. V/Q lung
scan vs. pulmonary
angiography
Acute myocardial
infarction
Serial enzymes (CK,

CK-MB, troponin T),
serial ECG, CXR
Congestive heart
Serial enzymes (CK,
failure
CK-MB, troponin T),
ECGs to rule out
acute myocardial infarction, CXR, echocardiogram
Muffled heart sounds, Cardiac tamponade Emergent bedside
Kussmaul sign (
echocardiogram
jugular venous
pressure during
inspiration), pulsus
paradoxus
ABG, arterial blood gas; CXR, chest X-ray; P2, pulmonic 2nd sound; PMI,
point of maximal impulse; PND, paroxysmal nocturnal dyspnea; V/Q, ventilation-perfusion.
114
I SIGNS & SYMPTOMS
Beware: history of intubation during exacerbation, elderly

patient, important comorbidities, history of steroid-induced
problems, hemodynamic instability
To ICU for noninvasive or invasive assisted ventilation if
pharmacologic therapy fails to reverse respiratory failure
(pH <7.30, PaO2 <55) and/or symptoms
Pneumonia
Oxygen to correct hypoxemia
Hydration
Antibiotics after sputum Gram stain/culture & blood cultures (2)
Antibiotic choice depends on severity of illness, etiologic factors, exposures, comorbidities, microbiology results,
drug resistance concerns, tolerability/side effects of drugs;
typical alternatives: fluoroquinolone, macrolide, or thirdgeneration cephalosporin
Likely pathogens for community-acquired pneumonia in
hospitalized patients
Streptococcus pneumoniae, Haemophilus influenzae,
polymicrobial, aerobic gram-negative bacilli, Legionella
sp. respiratory viruses
Consider Mycobacterium tuberculosis with upper lobe
infiltrates and/or high-risk patients
Consider aspiration if altered mental status, bulbar
weakness, alcohol abuse
Chest tube if empyema
Acetaminophen (1 g PO 2-4 times/day as needednot to
exceed 4 g/day)
Chest physiotherapy
Pulmonary Embolism
Heparin (80 U/kg IV bolus, followed by infusion of 18 U/kg
per hour)
If clinical suspicion for venous thromboembolism is high,
begin heparin before confirmatory testing if no contraindications (e.g., intracranial disease, recent surgery,
115
history of sensitivity to heparin products, active bleeding,

blood dyscrasias).
Recheck aPTT in 4-6 hours, titrate infusion to goal of 6090 seconds.
If clinical deterioration, consider bedside transthoracic
echocardiogram to evaluate for right ventricular strain and
then thrombolysis or surgical thrombectomy.
Pneumothorax
Tension pneumothorax is a clinical diagnosis and medical
emergency.
If suspected, do not wait for chest X-ray, use 14-16gauge needle to aspirate at 2nd intercostal space in mid-clavicular line.
Symptomatic or large pneumothoraces without tension
require chest-tube drainage.
Acute Myocardial Infarction

Transfer patient to ICU or coronary care unit as soon as
possible.
Oxygen
Aspirin (325 mg PO or rectally)
Morphine (2-4 mg IV as needed until pain is relieved)
Angiotensin-converting enzyme inhibitor
-Blocker
Nitrates
Thrombolysis vs. percutaneous transluminal coronary
angioplasty
Congestive Heart Failure

Oxygen
Restrict salt and fluid intake, bedrest, prophylaxis for deep
venous thrombosis
Furosemide IV, follow daily weight and input/output
Angiotensin-converting enzyme inhibitors
Consider digoxin.
Determine cause(s) or precipitating factor(s) for heart failure.
116
I SIGNS & SYMPTOMS

ELECTROLYTE DISTURBANCES
Lawrence K. McKnight, M.D.
NORMAL FLUIDS
Values for fluids are given in Tables 1 and 2.
HYPONATREMIA
Severity of symptoms and treatment depend on degree of
hyponatremia and on rate of onset.
Rapid correction results in central nervous system swelling
and central pontine myelinolysis.
This is worse than the hyponatremia.
Look for mental status changeslethargy, anorexia,
headache, vomiting, agitation, severe weakness, disorientation, coma, seizures.
Check previous lab values, if available, to evaluate progression.
Sodium levels <110-115 mEq/L are generally severe, but
this depends on rate of decline.
Addressing the Risk
If there are mental status changes and hyponatremia is acute,
correct more rapidly, up to 1 mEq/hour, and up to half the
deficit in the first 24 hours (see Management).
Find and treat the underlying cause.
The differential diagnosis for hyponatremia is listed in
Table 3.
Special abbreviations used in this chapter: DI, diabetes insipidus; TTKG,

transtubular potassium gradient.
117
Table 1. Values for Ionic Composition of Normal Fluids*
Fluid
Sweat/
burns
Saliva
Stomach
Na+ Cl
50
K+
Quantity/24 Normal replaceHCO3 hours ment, mL/mL
40
60 15
80 100
36
10
50
0
Duodenum 130 90
Bile
145 100
5
5
0-10
15
Pancreas
145
75
115
Ileum
Diarrhea
140 100
120 90
2-8
25
30
45
--
LR
1.5 L
-1.5-2.5 L D5 21 NS +
20 mEq K+
0.3-2 L -0.1-0.8 L D5LR + 25
mEq HCO3
0.1-0.8 L D5LR + 50
mEq HCO3
0.1-9 L --D5LR + 15
mEq K+
D5LR, 5% dextrose in lactated Ringer solution; LR, lactated Ringer solution;

NS, normal saline.
*Ionic values in mEq/L.
Table 2. Contents of IV Fluids

IV fluid
D5
D50
Normal saline
LR
Contents
50 g glucose/L = 170 kcal
500 g glucose/L = 1,700 kcal
154 mEq Na+, 154 mEq Cl
130 mEq Na+, 110 mEq Cl, 4 mEq K+,
3 mEq Ca+, 27 mEq HCO3 per liter
D5, 5% dextrose; D50, 50 g/dL dextrose; LR, lactated Ringer solution.

Hyponatremia is divided into hyperosmotic, isosmotic, and
hypo-osmotic conditions (hypo-osmotic is most common).
First step in evaluating hypo-osmotic hyponatremia is to
assess fluid balance.
If the patient is hypovolemic, check spot urine sodium to
differentiate renal from nonrenal loss.
If the patient is euvolemic, the cause is likely syndrome of
inappropriate antidiuretic hormone, but this is a diagnosis
of exclusion after thyroid, renal, and adrenal functions
have been checked.
If hypervolemic, the cause is likely heart, liver, or renal failure.
118
I SIGNS & SYMPTOMS

Table 3. Differential Diagnosis for Hyponatremia
Condition
Suspect when...
Hypovolemic
Orthostatics, skin turgor, BUN:Cr ratio
Renal losses (urine Renal tubular acidosis, polycystic kidney,
Na >20 mEq/L)
interstitial nephritis, pyelonephritis,
obstruction, diuretics, adrenal
insufficiency
Note: hypokalemia & HCO3 loss can
potentiate hyponatremia
Nonrenal (urine
Na <10 mEq/L)
GI losses
Vomiting, diarrhea, fistulas
Third space
Pancreatitis, peritonitis, burns
Osmotic
Mannitol
diuresis
Euvolemic
SIADH
ADH; low normal serum osmolarity
& blood pressure; normal renal,
adrenal, thyroid function
Cancerlung, duodenum, pancreas,
brain, bladder, prostate, lymphoma
Pulmonarypneumonia, asthma, TB
Braintrauma, infection, hemorrhage,
sarcoidosis
Medications
Chlorpropamide
Thiazide diuretics
TCAs and/or MAOI
Nicotine
Cyclophosphamide, vincristine,
vinblastine
Morphine, indomethacin (Indocin),
acetaminophen (Tylenol)
Haloperidol (Haldol), chlorpromazine
(Thorazine), barbiturates
Carbamazepine (Tegretol)
Vasopressin
AIDS
Hypothyroid
Decreased deep tendon reflexes, toad face
Primary polyHistory of excessive water intake
dipsia
119
Table 3 (continued)
Condition
Hypervolemic
CHF
Cirrhosis
Renal failure
Pseudo hyponatremia (osmolality
is normal)
Lipids
Proteins
Hyperosmolar
(osmolality >300
mOsm/kg)
Lab error
Suspect when...
Edema, jugular venous pressure
Rales, S3
Ascites, jaundice
Nephrosis, increased creatinine
Uncontrolled diabetes mellitus,

familial
Multiple myeloma
Infusions, diabetes mellitus
Osmolar gap (Osmmeasured Osmest) >10
Osmest = 2 [Na] + Glucose/18 + BUN/2.8
Diabetes mellitus (1.6 mEq Na per 100
mg/dL glucose)
Isolated value, asymptomatic patient
ADH, antidiuretic hormone; CHF, congestive heart failure; Cr, creatinine; GI,
gastrointestinal; MAOI, monoamine oxidase inhibitor; S3, third heart sound;
SIADH, syndrome of inappropriate antidiuretic hormone; TCA, tricyclic
amine.
Test Ordering
Check previous sodium value to determine rate of decrease.
If not explained by history, check serum chemistry panel,
serum osmolality, and spot urine electrolytes. Calculate
osmolar gap.
Depending on the history, consider checking sensitive thyrotropin, liver function tests, cortisol, lipids, and arterial
blood gases.
Management
If patient is hypovolemic, replete with normal saline.
If patient is euvolemic, then fluid restriction
Demeclocycline 300-600 mg PO twice daily for chronic syndrome of inappropriate antidiuretic hormone
Hypervolemic, sodium-restricted diet, furosemide
Severe hyponatremia can be corrected with hypertonic saline,
but this is rarely needed (remember, too rapid correction can
lead to central pontine myelinolysis).
120
I SIGNS & SYMPTOMS

Replacement Formula
Total body water (TBW) = weight (kg) 0.6 (males) or 0.5
(females, elderly)
Na deficit (mEq) = (desired [Na] measured [Na]) TBW
Note: correct 1/2 deficit over first 24 hours. Desired [Na]
is goal for the end of the day.
Free water excess = TBW [1 (measured [Na]/desired
[Na])] (= the amount negative fluid balance you are looking for)
IV fluid rate (mL/hour) = [Na deficit (mEq)/IV fluid Na concentration (mEq Na/L)] 1,000 mL/L 1 day/24 hours (3%
NaCl = 512 mEq Na/L, normal saline = 0.9% = 154 mEq Na/L)
HYPERNATREMIA
Hypernatremia, like hyponatremia, presents with neurologic abnormalities related to the acuity of change in sodium
concentration.
With acute increase and serum sodium >160 mEq/L, mortality rate is 75%.
Chronic changes are tolerated better and are correlated
with plasma osmolality.
Earliest signsrestlessness, irritability, lethargy
Later signs (plasma osmolality >375 mOsm)muscle spasticity, seizures, or death
Addressing the Risk
Therapy for symptomatic hypernatremia is listed below (see
Management).
Depending on severity of symptoms and rate of chance, correct the [Na] rapidly, as addressed in Management section.
Do not correct >2 mOsm/hour and total correction over 48
hours.
Find and treat the underlying cause.
The differential diagnosis for hypernatremia is listed in
Table 4.
121
Table 4. Differential Diagnosis for Hypernatremia

Condition
Hypovolemic
(H2O>Na+ loss)
Renal (urine
Na >20
mEq/L)
Nonrenal
(urine Na
<20 mEq/L)
GI
Insensible
Euvolemic
Central DI
(decreased
ADH)
Nephrogenic
DI (ADH
ineffective)
Reset osmolar
(maximally
concentrated
urine)
Insensible loss
Hypervolemic
Mineralocorticoid excess
Iatrogenic
Lab error
Suspect when...
Orthostatic, skin tenting
Diuretics (loop, thiazide, osmotic),
hyperglycemia, uremia, postobstructive
diuresis, polyuria, acute tubular necrosis
Vomiting, nasogastric suction, fistulas,

diarrhea
Fever (500 mL/day per C), sweating, burns
Intubation (may look euvolemic)
CNS insult (postoperative, trauma, infection, granuloma, tumor, metastases) with
restricted water access (intubated,
comatose)
Idiopathic
Chronic renal disease, medications
(lithium, sulfonylurea, analgesics,
amphotericin B, colchicine), Sickle cell
disease, polycystic kidney disease, hypokalemia, hypercalcemia, congenital
Hypothalamic brain lesion, hypodipsia,
pregnancy
As above, inability to drink

Cushing syndrome, exogenous steroids,
adrenal hyperplasia, ectopic ACTH
production, Conn syndrome
Salt tablets, dialysate error, postcode
(NaHCO3), tube feedings
Isolated value, asymptomatic patient
ACTH, corticotropin; ADH, antidiuretic hormone; CNS, central nervous system; DI, diabetes insipidus; GI, gastrointestinal.
122
I SIGNS & SYMPTOMS

Begin by evaluating the patients volume status.
Hypovolemic hypernatremia indicates free water loss in
excess of sodium loss.
Check spot urine sodium to distinguish between renal and
nonrenal loss.
Hypervolemic hypernatremia is uncommon and usually
iatrogenic.
Euvolemic hypernatremia is the most common presentation.
If not accounted for by insensible losses, water deprivation
test can be used to differentiate central from nephrogenic
diabetes insipidus (DI).
To perform this test, hold all fluids and check urine and
plasma osmolality every hour until plasma osmolality is
>288 mOsm/kg, weight is down 1-2 kg, and urine osmolality plateaus to within 30 mmol/kg for at least 3 hours
Next, give desmopressin, 1 g SQ or 10 g intranasally and
check urine and plasma osmolality in 1 hour.
Neither central DI nor nephrogenic DI will be able to concentrate urine with water deprivation.
Central DI will respond to vasopressin with >9% increase
in urine osmolality; nephrogenic DI will not.
Test Ordering
Check previous sodium value to determine rate of increase.
Urine sodium and osmolality
If hypo-osmolar urine, perform water deprivation test (see
above).
Depending on the history, consider serum chemistry panel,
calcium level, dexamethasone suppression test.
Management
If patient is hypovolemic, replenish with half normal saline.
If patient is euvolemic
If symptomatic, calculate free water deficit.
Free water deficit (L) = weight (kg) 0.6 [1 measured [Na] (mEq/L)/desired [Na] (mEq/L)]
Remember to include patients normal fluid requirements.
123
Replace half deficit with 5% dextrose or oral free water

over first 24 hours
Longer term specific therapy:
Central DIdesmopressin 10 g intranasally once or
twice daily
Nephrogenic DIhydroclorothiazide 12.5-50 mg PO
daily, low sodium diet
If patient is hypervolemic
Furosemide 5% dextrose
Dialysis if patient has renal failure
HYPOKALEMIA
If the patient has symptoms (decreased deep tendon reflexes, paralysis), potassium <2.5 mEq/L, or is receiving digoxin, obtain an ECG.
Look for flat T waves, U waves, increased QT, and arrhythmias.
Addressing the Risk
If evidence of digitalis intoxication or paralysis, admit patient
to ICU for ECG and respiratory monitoring.
Potassium can be administered IV up to 40 mEq/hour.
Monitor potassium level every 4 hours.
Avoid glucose- and alkali-containing solutions because they
can precipitate further hypokalemia.
The differential diagnosis for hypokalemia is listed in Table
5.

After historical exam, including medicine review and patient
symptoms, spot urine potassium test can help determine
renal cause from extrarenal loss.
If blood pressure is normal, ensure magnesium level is normal and look for low bicarbonate level to indicate acidosis.
If there is coexisting hypertension, check renin and aldosterone levels to distinguish between renal artery stenosis and
primary hyperaldosteronism.
124
I SIGNS & SYMPTOMS

Table 5. Differential Diagnosis for Hypokalemia
Condition
Renal loss (urine
K >20 mEq/day)
Hyperaldosteronism
Primary
hyperaldosteronism
Increased
renin
Mineralocorticoid
excess
RTA (low HCO3)
RTA 1 (distal)
RTA 2
(proximal)
Magnesium depletion
Volume depletion
Diuretics
Antibiotics
Extrarenal loss (urine
K <25 mEq/day)
GI
Cutaneous
Cellular shift
Inadequate intake (<20

mEq/day)
Pseudohypokalemia
Suspect when...
Hypertension (except Bartter syndrome)

(Low renin)
Renal artery stenosis, renin-secreting
tumor, Bartter syndrome
Conn syndrome, congenital adrenal
hyperplasia, licorice, Liddle syndrome
Hypercalcemia, renal stones, amphotericin B, connective tissue disease,
lithium, toluene
Inability to acidify urine
Multiple myeloma, heavy metals,
6-mercaptopurine, acetazolamide
Able to acidify urine
Tetany, cardiac arrhythmias
Vomiting (Na resorbtive state, alkalosis)
High urinary Cl
High-dose penicillin, carbenicillin
(anions)
Diarrhea, fistula, nasogastric suction
(alkalosis), laxative abuse, villous
adenoma, VIPoma, clay ingestion (clay
absorbs potassium & iron)
Fever
Alkalosis, insulin excess, -agonists
Hypokalemic periodic paralysis
Barium poisoning, digoxin immune FAB
(Digibind)
Leukemia, lymphoma
Rare
In whole blood, leukocytosis (>105/mL),
check serum potassium
GI, gastrointestinal; RTA, renal tubular acidosis.

125
Test Ordering
Check spot urine potassium to sort between renal (>20
mEq/day) and extrarenal causes.
If renal cause and normotensive, check bicarbonate level (to
look for renal tubular acidosis) and magnesium level.
If renal cause and hypertensive, check simultaneous renin
and aldosterone levels.
Depending on history, consider ECG, repeat serum potassium, arterial blood levels, digoxin level, diuretic screen.
Management
RoutePO preferred when possible.
Type
Acidosispotassium bicarbonate (or gluconate, acetate,
citrate)
Diabetic ketoacidosispotassium phosphate
All the restpotassium chloride
Quantity
Serum potassium decreases only when total body stores are
decreased by 100-200 mEq. Replace generously (Table 6).
Rate
PO 40-120 mEq/day
Peripheral vein 10-15 mEq/hour
Central line (femoral) 40 mEq/hour
Alternativesspironolactone, triamterene
Note
Replace more cautiously with renal impairment (creatinine
>3 mg/dL, BUN >45 mg/dL, creatinine clearance <30
mL/minute).
Avoid potassium-sparing diuretics and angiotensin-converting enzyme inhibitors.
Table 6. Potassium Replacement

Plasma potassium, mEq/dL
3.0-3.5
2.5-3.0
2.0-2.5
1.5-2.0
<1.5
126
Estimated replacement, mEq

100
200
350
500
800
I SIGNS & SYMPTOMS

Oral replacement can be associated with gastrointestinal
ulcers.
IV replacement burns and is associated with phlebitis.
For refractory hypokalemia, check and replace magnesium.
HYPERKALEMIA
If potassium is >6.5 mEq/L, obtain an ECG and place patient
on a monitor. Look for peaked T waves, wide QRS, depressed
ST segments.
Treat immediately based on ECG changes if present.
Otherwise repeat serum potassium measurement with arterial blood gases, calcium, magnesium, and electrolyte panel.
Addressing the Risk
If potassium is high (ECG changes, potassium >6.5 mEq/L),
treat immediately, as indicated in Table 7.
The differential diagnosis for hyperkalemia is listed in Table 8.

Most cases of hyperkalemia are due to decreased excretion.
First, ensure that the hyperkalemia is real and severe.
Obtain an ECG, and repeat serum potassium measurement.
If severe, treat empirically while searching for the cause.
Look for oliguria and renal insufficiency.
Stop angiotensin-converting enzyme inhibitors and NSAIDs.
Calculate the transtubular potassium gradient (TTKG)
TTKG = (urine K/plasma K) (plasma osmolality/urine
osmolality)
TTKG <10 indicates decreased excretion.
Give 0.2 mg fludrocortisone (Florinef), and repeat the
TTKG to differentiate hypoaldosteronism from aldosterone-unresponsive states.
A simultaneous renin and aldosterone level will help differentiate hyporeninemic hypoaldosteronism from primary
adrenal insufficiency.
127
128
Table 7. Treatment of Hyperkalemia

Drug
Duration
Mechanism
1-5 minutes
30-60 minutes
Membrane
stabilization
First-line therapy
30 minutes
2 hours
Redistribution
Give after calcium (can precipitate seizures

if hypocalcemic)
Do not give in same line as calcium because
it will precipitate
30-60 minutes
4-6 hours
Redistribution
1-2 hours
4-6 hours
Removal
Furosemide20-40 mg IV
15 minutes
4 hours
Removal
Hemodialysis
Immediate
Variable
Removal
Calcium gluconate10 mL of
10% solution over 2 minutes,
repeat every 5 minutes to effect
NaHCO3l ampule = 44.6
mEq over 5 minutes
Insulin/glucose15 U regular
in 50 mL of 5% dextrose
Sodium polystyrene sulfonate
(Kayexalate)15-30 mg PO
with 20 mL 70% sorbitol, or 30
mg prn in 200 mL H2O, repeat
every 4-6 hours prn
Action
Comment
50 mg will lower serum potassium by

0.5-1 mEq/L & will also raise sodium
by 1-2 mEq
Watch fluid balance
Constipating, give oral form with sorbitol, but
associated with intestinal necrosis in
postoperative patients, especially if given PR*
Watch fluid balance
Cautious use with renal insufficiency
Peritoneal dialysis is much less efficient
PR, per rectum; prn, as needed.

*Note that rectal administration of sodium polystyrene sulfonate is contraindicated for hemodynamically unstable patients.
I SIGNS & SYMPTOMS

Table 8. Differential Diagnosis for Hyperkalemia
Condition
Decreased excretion
Oliguric renal
failure
Hypoaldosterone (TTKG
>10 with fludrocortisone
[Florinef])
Primary hypoaldosteronism (increased
renin)
Hyporeninemic
(suppressed renin)
Aldosterone unresponsive
(TTKG <10 with fludrocortisone)
Tubulointerstitial
disease
Medications
RTA 4
Hereditary
Redistribution
Acidosis
Tissue breakdown
Insulin deficiency
Hyperkalemic periodic
paralysis
Medications
Excess intake
Pseudohyperkalemia
Suspect when...
TTKG >10, GFR <5 mL/minute
Dehydration, congestive heart
failure, NSAIDs, ACE inhibi-,
tors, protein malnutrition
Addison disease, congenital

adrenal hypoplasia, heparin
Sickle cell disease, SLE, renal

transplant, AIDS, multiple
myeloma
Potassium-sparing diuretics
(spironolactone, triamterene,
amiloride), trimethoprim,
pentamidine, cyclosporine
Diabetic glomerulosclerosis,
pyelonephritis, heavy metals
Gordon syndrome
Potassium 0.4 mEq, pH = 0.1
Tissue necrosis, tumor lysis,
hemolysis, hypercatabolism,
rhabdomyolysis
Autosomal dominant, intermittent
attacks last about 1 hour
Succinylcholine, digoxin toxicity,
-blockers, arginine, radiocontrast dye
TPN, penicillin (1 MU = 1.7 mEq
potassium), salt substitutes
(14 mEq/g)
Hemolysis, thrombocytosis
(>106), leukocytosis (>105)
ACE, angiotensin-converting enzyme; GFR, glomerular filtration rate; RTA,

renal tubular acidosis; SLE, systemic lupus erythematosus; TPN, total parenteral nutrition; TTKG, transtubular potassium gradient.
129
Hyporeninemic states also occur in renal tubular acidosis

and Gordon syndrome.
Test Ordering
ECG
Repeat serum potassium measurements with electrolyte panel
and BUN and creatinine.
TTKG and fludrocortisone trial
Simultaneous renin and aldosterone measurements
Depending on history, consider arterial blood gases, glucose, creatinine clearance, digoxin level, CK, aldolase.
Management
For acute hyperkalemia, treat emergently (as noted above).
For chronic hyperkalemia, treat underlying cause.
Hyporeninemic hypoaldosteronismfludrocortisone,
furosemide, or thiazide diuretic.
130
I SIGNS & SYMPTOMS

FEVER OF UNKNOWN ORIGIN
Ramona S. deJesus, M.D.
DEFINITIONS
Classic Fever of Unknown Origin (FUO)
Illness of at least 3 weeks duration
Temperature >101F (38.3C) on several occasions
No diagnosis after 1 week in hospital*
Nosocomial FUO*
Temperature 101F on several occasions in a hospitalized
patient receiving acute care
Neutropenic FUO*
Temperature 101F on several occasions
Neutrophils in peripheral blood <0.5 109/L (<500/mm3) or
expected to decrease to <0.5 109/L within 1-2 days
HIV-associated FUO*
Temperature 101F on several occasions in person with
serologically confirmed HIV infection

Immediate mortality for FUO is low, but some patients have
underlying diseases that are ultimately fatal.
Three most common causes of FUO are the following:
Infection (30%-40%)
Malignancy (20%-30%)
Collagen vascular disease (10%-20%)
*Revised defintion is no diagnosis after 3 days of inpatient investigation or 3

outpatient visits.
Special abbreviation used in this chapter: FUO, fever of unknown origin.
131
Look for stigmata of bacterial endocarditis.

Note degree of immunosuppression in patients with HIV
infection or neutropenia.
Consider agevisual disturbances with headache in person
>50 years may indicate giant cell arteritis.
Evaluate for signs of dehydration, especially with persistent fever and decreased oral intake.
Subtle behavioral changes may indicate central nervous system infection; perform a thorough neurologic exam.
ADDRESSING THE RISK

Routine and orthostatic vital signs, oxygen saturation
Hydration
Thorough physical exam
Initial testing (see below)
Discontinue all possible offending medications.
Look for localizing signs/symptoms.
Evaluate accordingly if nosocomial, neutropenic, or HIVrelated FUO.
The differential diagnosis of FUO is given in Table 1.
The causes of drug fever are listed in Table 2.

The history, lab, and physical exam findings for various causes of fever are listed in Table 3.
TEST ORDERING
Be sure that fever is documented before beginning expensive,
potentially invasive tests.
Take a careful history, including travel, immunizations, previous surgical procedures, exposure to animals/TB, alcohol
intake, familial disorders, history of any rash, HIV risk factors, tick bites, sexual preference).
Consider patients age.
On physical exam, check the eyes, including ophthalmoscopy,
lymph nodes, and entire skin and mucous membranes.
Unless another diagnosis is probable, consider drug fever
early and withdraw all medications the patient was taking
when fever began.
132
Table 1. Differential Diagnosis for Fever of Unknown Origin

Infections
Neoplasia
Endocarditis,* extrapulmonary/ Lymphomas, metastasis

miliary TB
to liver or central
nervous system
Intra-abdominal/GU abscesses
Cytomegalovirus, Epstein-Barr Myelodysplastic diseases

virus, zoonotic fevers, Lyme
disease
Malaria, fungal, dental abscess, Preleukemias, atrial
Kikuchi lymphadenitis,
myxomas
Whipple disease, salmonellosis
Miscellaneous
Drug fever, factitious fever,

habitual hyperthermia,
Castleman disease, familial
Mediterranean fever
Giant cell arteritis, polymyalgia Granulomatosis (e.g.,
rheumatica
sarcoidosis)
Systemic lupus erythematosus, Alcoholic hepatitis,
rheumatoid arthritis, Sjgren
hepatomas
disease, Reiter syndrome
Cryoglobulinemia, Behet
Pulmonary embolism
syndrome, mixed connective
tissue disorder
Hypersensitivity vasculitis,
Endocrine (thyroiditis,
other vasculitis (polyarteritis
hyperthyroid, ACTH
nodosa, Takayasu arteritis,
insufficiency), inflammatory
Wegener granulomatosis)
bowel disease
ACTH, corticotropin; GU, genitourinary.

*More likely culture-negative or hard-to-isolate organisms (e.g., Bartonella, Coxiella, HACKE).
133
I SIGNS & SYMPTOMS
Osteomyelitis, infected
prosthesis, HIV
Solid tumors (e.g., hypernephromas)

Lymphoproliferative
disease
Rheumatologic disorders
Still disease (adult)
Table 2. Causes of Drug Fever

Antibiotics (sulfonamides, penicillin, nitrofurantoin, antimalarial
agents)
Diuretics
Antiarrhythmics (quinidine, procainamide)
Antiepileptic drugs (phenytoin)
Antihistamine (H1 & H2 blockers)
Allopurinol
Sedatives (barbiturates)
Antihypertensives (hydralazine, methyldopa)
Bleomycin
Iodides
Antithyroid drugs
Initial tests (minimum recommended evaluation)

Lab testsCBC with differential; ESR; blood cultures
(bacterial, fungal) 3 off antibiotics; thyroid-stimulating
hormone (TSH); BUN/creatinine; routine blood chemistry panel (liver enzymes, LDH, bilirubin, serum calcium,
alkaline phosphatase, rheumatoid factor, antinuclear antibodies), urinalysis with microscopy; urine, stool, sputum
cultures; guaiac stools; HIV serology
Radiology testschest X-ray; abdominal CT/MRI;
CT/MRI of chest, pelvis, head (if appropriate); echocardiography
Tuberculin testing with control(s)
Invasive testsbiopsy of any suspicious lymph nodes or
skin lesions
Follow-up tests
Bone marrow biopsy if miliary TB or cancer suggested
Gallium 67/indium 111labeled leukocyte whole body
scans
Repeat CT/MRI with thinner sections to detect small
lesions
Transesophageal echocardiography (positive in >90% of
cases of infective endocarditis presenting as FUO)
Prolonged incubation of blood cultures
Polymerase chain reaction for Mycobacterium TB
Liver biopsy if suggested by diagnostic clues
Bronchoscopy/colonoscopy if indicated
134
I SIGNS & SYMPTOMS

Table 3. Cause of Fever Correlated With History, Lab, and
Physical Exam Findings
Cause
Infection
Subacute bacterial
endocarditis
History
IV drug use
Granulomatous
meningitis
Malaria
Subtle behavioral
changes
Fever every 2-3
days
Intra-abdominal
abscess
History of intraabdominal infections (hepatic,

pelvic, pancreatic,
subphrenic)
History of blood
transfusion,
immunosuppression
CMV
Lyme disease
Kikuchi lymphadenitis
Whipple disease
Tick exposure,
history of rash,
endemic location
Women <40 years
Triad of diarrhea
(malabsorption);
weight loss; transient, migratory,
recurring arthralgia
Lab & physical

findings
Osler nodes, new
regurgitant murmur, Janeway
lesions, splinter
hemorrhage
Microscopy of
stained thin &
thick blood films,
antigen detection
Localized tenderness
CMV IgM/viral
isolation from
blood, rash,
hepatomegaly,
splenomegaly
Lyme serology +
Enlarged cervical
lymph nodes,
neutropenia,
maybe abnormal
LFTs
Increased ESR
(>30 mm/hour)
135
Table 3 (continued)
Cause
Malignancy
Lymphoma
Hypernephromas
Rheumatologic
Still disease
History
Pel-Ebstein fever
(increased temperature for several
days alternating
with normal temperature), weight
loss, B symptoms
Hematuria, flank
pain
Lymphadenopathy,
splenomegaly,
increased LDH
Young (16-35
years), high fever,
myalgias, sore
throat, arthralgias
Evanescent, macular rash primarily

on trunk during
fever, increased
ferritin level
Increased ESR,
anemia, scalp
tenderness, abnormal palpable
temporal artery;
25% have increased alkaline
phosphatase
Mononeuritis
multiplex (in
60%), skin
lesions (palpable
purpura, livedo
reticularis), abnormal renal function
Minor/major
aphthous ulcers,
anterior uveitis,
erythema nodosum, positive
pathergy test/
urate crystal test
Giant cell arteritis
>50 years, headache, visual loss,

jaw claudication;
associated with
polymyalgia
rheumatica
Polyarteritis nodosa
Associated with
hepatitis C
Behet syndrome
Painful, recurrent
oral/urogenital
ulcerations,
arthralgias,
myalgias
136
Lab & physical

findings
Palpable mass,
hypercalcemia,
erythrocytosis
I SIGNS & SYMPTOMS

Table 3 (continued)
Cause
Miscellaneous
Adrenocortical
insufficiency
Castleman disease
Factitious fever
History
Nausea/vomiting,
weight loss
Lab & physical

findings
Hypotension, skin
hyperpigmentation
Peripheral lymphadenopathy with
anemia
Mostly <30 years

(for localized
form), painless
mass, B symptoms
Multiple hospitaliza- Healthy looking,
tions & diagnostic
fever lacks
testing
diurnal pattern
with rapid
defervescence
CMV, cytomegalovirus; LFT, liver function test.
Temporal artery biopsy to check for giant cell arteritis or

biopsy of infected area to diagnose vasculitic process (e.g.,
polyarteritis nodosa)
Exploratory laparotomy (rarely required with CT or percutaneous biopsy)
Despite meticulous investigation, the cause of FUO is not
discovered in 5%-15% of cases.
MANAGEMENT
Empiric antibiotic trials, except for culture-negative endocarditis, have no place in management of FUO.
Empiric antibiotic therapy is prudent for seriously ill or
deteriorating patients.
High-dose corticosteroid treatment should be given only to
patients with biopsy-proven vasculitis.
Particularly in elderly patients with suspected miliary TB,
empiric anti-TB therapy is acceptable, especially if patient
has an exposure history or known positive PPD.
137
FUO IN SUBPOPULATIONS
Nosocomial FUO
Diverse causes, underlying disease, and complications of
hospitalization must be considered.
Patients with known cancer (neutropenic-associated fever)
Infectious cause in 1/2 of cases reviewed, gram-negative
bacilli and gram-positive cocci or fungi the usual causes
(typically as complication of neutropenia)
Extension or progression of tumor also causes fever
Patients infected with HIV
Infectious in 75% of patients, usually with advanced disease (CD4 cell count <100/mm3 [<0.1 109/L])
Most common organismMycobacterium (M. tuberculosis or M. avium-intracellulare)
Other common organismscytomegalovirus, Toxoplasma
gondii (toxoplasmosis), Pneumocystis carinii, Cryptococcus
Non-Hodgkin lymphoma or drug fever in 10%
138
I SIGNS & SYMPTOMS

GASTROINTESTINAL TRACT BLEEDING
Amindra S. Arora, M.B., B.Chir.
IMMEDIATE EVALUATION AND MANAGEMENT

Initial focal pointhemodynamics
Presence of orthostatic tachycardia and/or hypotension (systolic blood pressure drop >10 mm Hg or heart rate increase
>15 beats/minute) or shock
Indicates moderate to massive blood lossthe patient is
at risk
Baseline hypertensive patientscan be normotensive
despite substantial blood loss
Patients with unstable vital signsoften bleeding from major
vascular source
Unstable patientspoorer prognosis than for those with normal vital signs
Other important cluesmental status changes, profuse
diaphoresis and intense pallor, cyanosis, and low oxymetry
levels. Do not miss!
Hemodynamic instabilitywarrants immediate resuscitation efforts and call for assistance
Addressing the Risk
Resuscitationshould take precedence over diagnostic or
therapeutic procedures that could place patient at higher risk
Goalrestore and maintain normal vital signs
Key importanceimmediate and constant assessment of
vital signs
Special abbreviations in this chapter: GI, gastrointestinal; PPI, proton pump

inhibitor.
139
General management of all unstable patients must include the

following:
Two large-bore (18 gauge) peripheral intravenous catheters
Rapid infusion of colloid (normal saline or lactated Ringer
solution) as tolerated per comorbidities
Transfusionsvirtually all unstable patients need packed
RBCs; if actively bleeding and coagulopathic (INR >1.5
or platelets <50,000 mm3 [50 109/L]), transfuse fresh
frozen plasma and platelets, respectively
Supplemental oxygen
Monitoring of vital signs and urine output
ICU monitoringhigh risk for adverse outcomes include
patients who do not respond to initial resuscitation
measures and have greater prevalence of significant
comorbidities
Surgery consultation if patient refractory to initial resuscitation, requires >4 units RBCs over 24 hours, has massive active bleeding, has recurrent bleeding
Do not use nasogastric lavage to assess bleeding activity;
vital signs are more effective.
Early diagnostic and therapeutic procedures should be instituted and may alter prognosis, especially with upper gastrointestinal (GI) tract bleeding. Always follow assessment
of hemodynamic stability and adequate resuscitation.
General measuresconsider endotracheal intubation for
aspiration prevention, especially if patient has altered mental status, massive hematemesis, and variceal hemorrhage.
The differential diagnosis for GI tract bleeding is listed in
Table 1.
The presentation typical of upper and lower GI tract bleeding sites is listed in Table 2.
The risk factors for various conditions producing GI tract
bleeding are listed in Table 3.
History and physical exam (Table 4)
Important in assessing severity of bleeding and making a
preliminary assessment of the site and cause of bleeding
Are rarely diagnostic of the source of bleeding
140
I SIGNS & SYMPTOMS

Table 1. Differential Diagnosis for Gastrointestinal (GI)
Tract Bleeding
Site
Nasopharyngeal bleeding
Pulmonary hemorrhage
GI bleeding
Upper tract (proximal to
ligament of Treitz)
Lower tract (distal to

ligament of Treitz)
Anorectal bleeding
Condition
Epistaxis
Gingival bleeding
Airway disease
Pulmonary parenchymal disease
Pulmonary vascular disorders
Miscellaneous pulmonary or
systemic disorders
Peptic ulcer disease
Esophagogastric varices
Mallory-Weiss tears
Mucosal erosions
Arteriovenous malformation
Neoplastic
Other: Dieulafoy lesions, portal
hypertensive gastropathy, gastric
antral vascular ectasia (watermelon stomach), perforated/
ruptured esophagus (Boerhaave
syndrome), hemobilia, hemosuccus pancreaticus, aortoenteric
fistula
Diverticulosis
Angiodysplasia
Radiation-induced
Vasculitis
Ischemic colitis
Infectious colitis
Neoplastic
Polyps
Other: postpolypectomy/biopsy,
stercoral ulcers, aortocolonic
fistula, anastomotic bleeding,
intussusception, Meckel diverticulum, portal colopathy &
colonic varices, endometriosis,
Dieulafoy lesions
Hemorrhoids
Fissure
Idiopathic rectal ulcers
141
Upper GI tract bleedingapproximately 5 times more common than lower GI tract bleeding
Patients with upper GI tract bleeding are more likely to be
hemodynamically unstable at presentation because of severe
blood loss and to require blood transfusions than patients
with lower GI tract bleeding.
Patients with unstable vital signs are often bleeding from a
major vascular source, such as an ulcer with a visible vessel
or gastroesophageal varices.
Ordering Tests
All Patients
Complete CBC
Initial hemoglobin or hematocrit may not reflect the degree
of blood loss
Serial measurements (every 6 hours) are recommended.
Type and crossmatch
Electrolytes
BUN/creatinine especiallyWatch for disproportionate
increase in BUN:creatinine often seen in upper GI tract
bleeding.
Poor renal function is an indication of higher risk patient
Coagulation profile (INR, platelets)
Upper and Lower GI Tract Bleeding
Initial evaluation with suggestive history and physical exam
Nasogastric aspirate has no role in distinguishing between
upper and lower GI tract bleeding.
Table 2. Usual Clinical Presentation of Gastrointestinal

(GI) Tract Bleeding
Bleeding site
Upper GI
tract
Lower GI
tract
Presentation
Hematemesis
Vomiting of bloodfresh bright

red blood or old, coffee-grounds
appearance
Melena*
Black, tarry, foul-smelling stools
Hematochezia Bright red blood from rectum
*Melena can result from distal small bowel or even ascending colon bleeding,
especially with high colonic transit time.
About 10% of patients with upper GI tract bleeding present with hematochezia.
142
I SIGNS & SYMPTOMS

Table 3. Risk Factors
Risk factor
Advanced age
Younger age
Known liver disease
Known gastrointestinal
disease, previous
bleeding
Helicobacter pylori
Acute nonbleeding
critical illness
Increased gastric acid
production
NSAIDs/aspirin
Ethanol ingestion
Abdominal pain
Previous surgery
Radiotherapy
Hepatic parenchymal or
biliary tract injury
Retching/vomiting
Weight loss/anorexia,
change in bowel habits
Condition
Diverticula, ischemic colitis, neoplastic
PUD, esophagitis, varices, Meckel
diverticulum
Portal hypertension, esophagogastric
varices/portal hypertensive gastropathy
Diverticular disease, ulcer disease,
hereditary hemorrhagic telangiectasia,
inflammatory bowel disease
PUD, neoplastic
PUD
PUD
Gastroduodenal ulceration, colitis,
diverticular bleeding, pill-induced
esophagitis
Erosive esophagitis, PUD
PUD, mesenteric and/or colonic
ischemia
Aortic surgery & aortoenteric/
aortocolonic fistula, colon resection &
anastomotic bleeding
Radiation colitis/proctitis, radiationinduced telangiectasia
Hemobilia
Mallory-Weiss tears, esophageal rupture
Neoplastic
PUD, peptic ulcer disease.
143
Table 4. History and Physical Exam Findings Associated

With Various Causes of Gastrointestinal Tract
Bleeding*
Etiology
Physical exam
History
Peptic ulcer
disease
Epigastric tenderness History of epigastric pain,

GERD, NSAID/aspirin
use, alcohol ingestion,
tobacco use
Portal hyperten- Cutaneous signs
History of alcohol abuse
sion/esophago- (spider angiomata,
gastric varices Dupuytren contractures, palmar
erythema), splenomegaly, ascites,
caput medusae
Mallory-Weiss
Retching/vomiting
tear
Vascular
Telangiectasias of
History of hereditary
skin & mucous
hemorrhagic telangiecmembranes
tasia
Erosive
Alcohol, NSAID/aspirin
use, tobacco use, GERD
Neoplasia
Acanthosis nigricans, Weight loss, dysphagia
(gastric)
Virchow node,
Sister Mary Joseph
nodule, Blumer
(rectal) shelf
Neoplasia
Pallor
Weight loss, bowel-habit
(colonic)
changes, iron deficiency
anemia
Ischemic colitis Normal physical
Previous hypotension,
exam + severe
shock
abdominal pain
Postpolypectomy
History of recent
colonoscopy/polypectomy
Aortocolonic/
History of previous aortic
aortoenteric
graft surgery
fistulas
Stercoral ulcers
Chronic constipation
Radiation
Previous radiotherapy
colitis
(pelvic/prostatic)
GERD, gastroesophageal reflux disease.
*Historical information or physical findings will not be present all the time.
144
I SIGNS & SYMPTOMS

Upper GI Tract Bleeding
Upper endoscopy
Diagnostic modality of choice for acute upper GI tract
bleeding
Highly sensitive and specific for locating and identifying
bleeding lesions and is potentially therapeutic
Barium radiography is not recommended in acute upper GI
tract bleeding.
Lower GI Tract Bleeding
Colonoscopyinitial exam of choice for diagnosis and
treatment
Radiographic studies (plain abdominal films)should precede colonoscopy if perforation or obstruction is suspected
Anoscopy and sigmoidoscopy
Can be useful for diagnosis of anorectal and left colon
bleeding sites but do not rule out synchronous lesions
Role unclear if colonoscopy readily available
Other possibly useful diagnostic proceduresradionuclide
imaging and mesenteric angiography
Radionuclide imaging
Detects bleeding at a rate of 0.1-0.5 mL/minute
Is more sensitive than angiography but less specific than
positive endoscopy or angiography
Disadvantagespoor localization and nontherapeutic
procedure
Can be used before angiography to determine which
patients are bleeding sufficiently to make a positive angiographic result likely
Angiography
Requires active bleeding at a rate of 1-1.5 mL/minute to
be positive
Potentially therapeuticvasopressin infusion and
embolization can be performed through the catheter
Has a role in patients in whom endoscopy is not feasible
and in those with persistent or recurrent bleeding and nondiagnostic colonoscopic findings
145
Barium studies have no role in evaluation of acute lower GI

tract bleeding.
Initial Management of GI Tract Bleeding

The initial management is outlined in Table 5.
PEPTIC ULCER DISEASE
Endoscopy with therapeutic procedure in high-risk lesions
Early use of proton pump inhibitor (PPI)pantoprazole, 80
mg IV bolus, 8 mg/hour infusion over 24 hours, then pantoprazole, 40 mg/day PO, or omeprazole, 20 mg/day PO, or
if IV PPI not available, high-dose oral PPI (e.g., omeprazole, 40 mg PO twice daily)
Rebleeding after successful endoscopysecond endoscopic treatment
Surgery
If bleeding is not responsive to standard therapy
For recurrent bleeding after second endoscopic procedure
If poor surgical candidate, angiographic therapy
If endoscopy is unavailable, contraindicated, or unsuccessful, some evidence for treatment with somatostatin, 250 g
bolus then every hour for 3-7 days, or octreotide, 10-50 g
bolus + 25 g/hour up to 3 days
Prevention of recurrencetreat underlying disease (eradicate
H. pylori, discontinue NSAIDs)
ESOPHAGOGASTRIC VARICES
Octreotide, 50 g bolus followed by 50 g/hour IV infusion
for 5 days, or somatostatin, 250 g bolus followed by 250
g/hour IV infusion for 5 days; plus
Table 5. Initial Management of GI Tract Bleeding

Alwaysassess hemodynamic stability & resuscitate if needed!
Keep in mindthere is evidence that in most patients bleeding
stops without any intervention
Preparation for endoscopy
Nasogastric or orogastric lavage to remove particulate matter, fresh blood, & clots to facilitate procedure & decrease
risk of aspiration
Erythromycin IV 3 mg/kg over 20-30 minutes, 30-90 minutes before endoscopy
146
I SIGNS & SYMPTOMS

Endoscopy with band ligation (esophageal varices) or
sclerotherapy
If initial therapy fails, a second endoscopic trial is reasonable;
balloon tamponade is also effective for achieving short-term
hemostasis (Sengstaken-Blakemore tube, Minnesota tube,
or Linton-Nachlas tube).
Persistent or recurrent bleeding may require more definite
therapyeither transjugular intrahepatic portosystemic stent
shunt or surgery (shunt-surgery procedures).
General management for variceal bleeding includes
Aspiration preventionairway protection and gastric
decompression by nasogastric aspiration
Infection prophylaxis
Usually quinolone (ofloxacin, 400 mg; norfloxacin,
400-800 mg; ciprofloxacin, 400-1,000 mg) for 7-10 days;
initially IV, followed by completion with administration PO
Optimal choice of drug and duration of therapy are not
clear.
Treatment of hepatic encephalopathylactulose
Avoidance of renal failureappropriate volume replacement, avoidance of nephrotoxic drugs
Primary prophylaxispropranolol or nadolol (dosage as tolerated, decrease resting heart rate 25%)
Secondary prophylaxisband ligation or sclerotherapy with
or without propranolol or nadolol (controversial subject)
MALLORY-WEISS TEARS
Endoscopic therapyindicated for actively bleeding lesions
or for patients with bleeding stigmata
No definite evidence for treatment with PPIs
ESOPHAGITIS
Treatment of underlying causehigh-dose PPI
Endoscopic therapyif ulcerations and/or visible vessels
COLONIC DIVERTICULA
Colonoscopy for recurrent bleeding, with endoscopic therapy
for bleeding lesion or bleeding stigmata
147
Recurrent bleedingusually requires combination of colonoscopic treatment, angiographic intervention, and surgical
resection of identified site
Poor outcome after blind subtotal colectomy, especially in
elderly
ANGIODYSPLASIAS
Upper endoscopy/colonoscopy, with endoscopic therapy for
bleeding lesion or bleeding stigmata
Angiography in cases of continuing or recurrent bleeding;
therapeutic intervention with intra-arterial vasopressin or
embolization
Surgeryrarely necessary
HEMORRHOIDS
Nonsurgical management is usually effectivesitz baths,
avoidance of straining and stool softeners, dietary modifications.
Because of high prevalence, rule out other causes of bleeding, especially in patients >50 years.
Refractory diseasetherapeutic options are rubber-band
ligation, coagulation therapy, surgical hemorrhoidectomy.
148
I SIGNS & SYMPTOMS

HEADACHE
Douglas J. Creedon, M.D.
Anna M. Georgeopolus, M.D.
J. D. Bartleson, M.D.
Headache
Common reason patients present to emergency department; can be common complaint of hospitalized patients
Initial evaluation should include following life- or
neurologic function-threatening secondary causes of
headache:
Subarachnoid hemorrhagetypically from ruptured
aneurysm or arteriovenous malformation
Intracerebral hemorrhage usually hypertensive
Ischemic strokeembolism, thromboembolism,
stenosis, dissection
Meningitis
Giant cell arteritiscan cause sudden irreversible
blindness
Epidural or subdural hemorrhageoften with trauma
history
Enlarging brain masstumor, abscess, aneurysm
Pituitary apoplexy
The history often provides the best clue to headache cause.
Warning signs are listed in Table 1.
ADDRESSING THE RISK
First step in ruling out life-threatening causes of headache
neuroimaging
If intracranial bleeding (subarachnoid hemorrhage, hemorrhagic stroke, posttraumatic bleeding) is a consideration
Immediate noncontrast CT of head should be performed.
Acute blood will appear bright.
If this is negative, as in approximately 5% of subarachnoid
hemorrhages, proceed to lumbar puncture.
149
Lumbar puncturegold standard for evaluating blood

in the CSF, look for xanthochromia
To guard against being misled by a bloody tap, the RBCs
in both the first and last tubes of CSF should be assayed.
Do not perform lumbar puncture on patient with signs of a
mass or increased intracranial pressure (midline shift, blunting of gyri on CT) because sudden release of pressure can
cause brainstem herniation and death.
If pituitary apoplexy is part of the differential diagnosis,
examine coronal CT slices.
After potentially life-threatening causes of headache have
been addressed, consider a more extensive differential list
(Table 2).
History is keymany migraine patients know they are having a migraine and are able to tell you what has and has not
worked in the past.
Table 1. Warning Signs in the Headache History

Think of the following
If you hear
Subarachnoid hemorrhage Worst headache of my life

Sudden onset, thunderclap headache
(timing is more telling than severity)
Stiff neck
Mass
Increasing frequency or duration of
headaches
New-onset headache in patients >50
years
New-onset neurologic signs or
symptoms (e.g., weakness, visual
disturbances)
Giant cell arteritis, cereHeadaches in elderly (>60 years)
brovascular accident
Intracranial bleeding
History of trauma (may be several
weeks past & a mild injury, especially
in elderly, alcoholics, & patients
taking anticoagulants)
Meningitis
Stiff neck, especially if associated
with fever
Mass, cerebrovascular
Weakness, numbness, or specific
accident
neurologic deficits
150
I SIGNS & SYMPTOMS

Table 2. Differential Diagnosis for Headache
Primary headache disorders
Migraine headache
Tension headache
Cluster headache
Secondary causes of headache
Systemic illness
Giant cell (temporal) arteritis
Meningitis
Subarachnoid hemorrhage
Subdural hemorrhage
Epidural hemorrhage
Stroke
Tumors
Metastases: lung, breast, melanoma
Primary tumors: gliomas, meningiomas, pituitary adenomas
Hypertension (usually >200/120 mm Hg)
Carotid dissection
Vertebrobasilar insufficiency
Cerebral venous thrombosis
Pseudotumor cerebri
Trauma, including posttraumatic headaches
Cholesteatomas
Brain abscess
Hydrocephalus
Sinusitis
Dental abscess
Acute-angle closure glaucoma
Temporomandibular joint disorders
Postherpetic neuralgia
Trigeminal neuralgia
Carbon monoxide poisoning
Prescription drug-induced headache
Rebound withdrawal headaches
151

A chief complaint of headache or new development of
headache warrants a complete neurologic exam, including
ophthalmoscopic exam.
Often, even life-threatening secondary causes of headaches
can present with a paucity of physical signs.
When evaluating a headache, consider the following: location, quality, radiation, severity (scale of 1-10), temporal
profile, exacerbating factors, ameliorating factors, and associated symptoms (Tables 3 and 4).
Table 3. Symptoms That May Be Associated With Certain

Causes of Headache
If yes, consider
Did the headache begin abruptly?
Is the headache associated with
new neurologic signs or symptoms?
Is the headache associated with fever
or myalgias?
Is the headache worsened by coughing
or Valsalva maneuver?
Mass lesion, stroke, or
giant cell arteritis
Meningitis
Mass, increased intracranial pressure, ArnoldChiari malformation
Mass lesion
Does the headache awaken patient

from sleep?
Is the headache bandlike?
Tension headache
Does patient have a history of cancer? Metastasis
Is the headache associated with nausea Mass lesion (especially in
& vomiting?
posterior fossa),
vertebrobasilar cerebrovascular accident
Does patient have scalp tenderness,
jaw claudication, malaise, arthralgias,
or polymyalgia rheumatica?
Do any visual or auditory changes
Migraine
precede the headache?
Migraine, meningitis
photophobia or phonophobia?
Is the pain sharp and lancinating?
Trigeminal neuralgia,
cluster headache,
postherpetic neuralgia
Do eating, drinking, or tooth
Trigeminal neuralgia,
brushing trigger the headache?
temporomandibular joint
dysfunction
152
I SIGNS & SYMPTOMS

Table 3 (continued)
If yes, consider
Is there a history of facial grimacing?
lacrimation or rhinorrhea
(especially one-sided)?
Do the headaches come in bunches,
followed by headache-free periods?
Is the patient immunosuppressed
or immunocompromised?
Cluster headache
Cluster headache,
trigeminal neuralgia
Infection (cryptococcosis,
histoplasmosis, toxoplasmosis), primary
central nervous system
lymphoma
Table 4. Signs That May Be Associated With Certain

Causes of Headache
If on exam you find
Consider
Horner syndrome (ptosis,

miosis, anhidrosis)
Papilledema
Cluster headache, carotid dissection
Bitemporal field loss

Focal motor or sensory
deficits
Disorientation or depressed
level of consciousness
Mass lesion, pseudotumor cerebri,

cerebral venous thrombosis
Pituitary mass, suprachiasmatic
lesion (e.g., craniopharyngioma)
Mass lesion, stroke, cerebral venous
thrombosis
Mass lesion, toxic metabolic disease,
cerebral venous thrombosis,
epidural or subdural hematoma,
subarachnoid hemorrhage
TEST ORDERING
The tests should be dictated by the differential diagnosis.
Some tests that may prove helpful, and the indications for
each, are listed in Table 5.
MANAGEMENT
Management for some causes of headache is given in Table 6.
153
Table 5. Tests to Order When Working Up a Headache

If your differential includes
Consider the following test
Head CT without contrast (with

contrast, if suspicion of mass is
high), lumbar puncture
Subarachnoid hemorrhage,
CSF analysis: glucose, protein,
meningitis
RBCs, WBCs, and cultures or
polymerase chain reaction (e.g., for
herpes simplex virus) if indicated
Metastasis, infection, drugs
Blood tests: CBC, electrolytes,
or toxins
glucose, carbon monoxide levels
(and other toxins if suggested by
history)
Infection, drugs or toxins
Urinalysis, especially in elderly
Mass lesion
CT without and with contrast, MRI
if CT is negative & suspicion is
high or if CT shows mass lesion
that cannot be characterized
ESR, temporal artery biopsy (do not
wait to begin treatment if suspicion
for giant cell arteritis is high;
steroids will not affect biopsy
results if the biopsy is performed
within 48 hours after starting
therapy)
Cerebral venous thrombosis, MRI with gadolinium, magnetic
encephalitis (e.g., infection) resonance venography
154
I SIGNS & SYMPTOMS

Table 6. Management of Some Causes of Headaches
Subarachnoid hemorrhage Pain management
Antiemetics for nausea
Monitor blood pressure & maintain at
or below normal
Neurovital signs every 2 hours;
maintain NPO
Call neurosurgery to clip/coil
Control vasospasms (days 4-14 after
hemorrhage) with nimodipine
Meningitis
Bacterial
Head CT without contrast
Lumbar puncture if CT is negative (do
lumbar puncture first if suspicion is
high)
If CSF is positive for bacteria,
cefotaxime
Viral
Supportive treatment, antiviral for
herpes simplex
Tension headache
Analgesics (e.g., ibuprofen, parenteral
ketorolac)
Migraine headache
The key is to use whatever is needed to
break the headache. Try the following
in descending order:
Triptan of choice (e.g., sumatriptan)
NSAIDparenteral ketorolac
Opioid analgesics (PO or parenteral)
Dihydroergotamine mesylate (DHE
45)do NOT mix triptans,
DHE 45 & other ergots
Chlorpromazine
IV fluids if patient has not been able
to eat/drink
Triptans, dihydroergotamine & other
ergots are contraindicated in
pregnancy, severe hypertension,
& known or suspected coronary
artery disease
Migraine headache in
Meperidine
pregnancy
Promethazine
155
Table 6 (continued)
Cluster headache
Brain mass
Pseudotumor cerebri
156
Sumatriptan, usually SQ
100% oxygen through nasal cannula or
nonrebreather at 7-10 L/minute for
10-15 minutes
Dihydroergotamine, usually
parenterally
Prednisone
Schedule temporal artery biopsy
within 48 hours
Carbamazepine
Dexamethasone
Chest X-ray, CT of chest & abdomen
to look for primary tumor
Neurology & neurosurgery consults
Serial lumbar punctures to decrease
intracranial pressure
Acetazolamide
Prednisone
Weight loss
I SIGNS & SYMPTOMS

HEMATURIA
Amy S. Oxentenko, M.D.
Fernando C. Fervenza, M.D.

Normal urinalysis can include <3 RBCs per high-power field
of centrifuged urine.
Hematuria, either microscopic or macroscopic, is defined as
3 RBCs per high-power field.
In very few circumstances is hematuria deemed life-threatening, but such circumstances do exist and need prompt
recognition to prevent morbidity or mortality.
Acute Conditions and Associated Findings
Renal traumaposterior rib fractures, flank ecchymosis,
hypotension, penetrating injury below the nipple line
Renal infarction (embolic vs. thrombotic)irregular heart
rhythm, new murmurs, livedo reticularis, blue toes, recent
angiography, recent myocardial infarction, multiorgan dysfunction, severe hypertension, flank/abdominal bruits
Accelerated hypertensionmental status changes, visual
impairment, headache
Severe bleeding diathesispallor, ecchymosis, oozing from
other sites
Sickle cell crisisAfrican American, dehydration, infection, diffuse pain
Subacute Conditions and Associated Findings

Renal vein thrombosishistory of clotting disorder, history of
nephrotic syndrome or paroxysmal nocturnal hemoglobinuria
Glomerulonephritidesarthralgias or arthritis, skin rashes or
Special abbreviations used in this chapter: ANA, antinuclear antibody; ANCA,

antineutrophil cytoplasmic antibody; ASO, antistreptolysin O; ENA, extractable
nuclear antigen; GBM, glomerular basement membrane; MPO, myeloperoxidase.
157
lesions, hypertension, edema, oliguria, history of pharyngitis

or pyoderma
Multisystem disorders (systemic lupus erythematosus,
microscopic polyangiitis, Wegener granulomatosis,
Goodpasture syndrome, scleroderma, Henoch-Schnlein
purpura, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura)rashes, arthralgias or arthritis,
neuropathies, rhinosinusitis, hemoptysis, sclerodactyly,
abdominal pain, melena, recent diarrheal illness
Arteriovenous fistulasabdominal/flank bruits, tachycardia
Pyelonephritisfever, costovertebral angle tenderness
Bladder, ureteral, or urethral traumablood at meatus, pelvic
trauma or fracture
Enterovesical fistulafecaluria, pneumaturia
ADDRESSING THE RISK

If gross hematuria
Stabilize blood pressure.
IV fluids to hydrate and prevent obstruction from clotting
CBC, type and crossmatch, coagulation studies (PT/INR,
PTT), peripheral blood smear
Creatinine to evaluate renal function
Dipstick, then formal urinalysis, with cultures as directed
C3, C4, CH50, antistreptolysin O (ASO), ESR, antinuclear antibody (ANA), extractable nuclear antigen (ENA)
panel, antineutrophil cytoplasmic antibody (ANCA),
antimyeloperoxidase (MPO), antiproteinase 3,
antiglomerular basement membrane (GBM), cryoglobulins.
Reverse coagulopathy if present.
Trauma
CT kidneys/pelvis
Retrograde urethrography if blood at meatus
Suspected renal artery or vein thrombosis or embolism
Renal ultrasound with Doppler studies vs. CT, depending on availability
Magnetic resonance angiography
Renal arteriography
Seek critical carerefractory hypotension, severe hypertension, fulminant hemolysis, acutely compromised renal
function, multiorgan dysfunction
158
I SIGNS & SYMPTOMS

DIFFERENTIAL DIAGNOSIS FOR HEMATURIA
The differential diagnosis is given in Table 1, and the causes
of hematuria are listed by age and sex in Table 2. The history,
physical exam, and lab findings for various causes of hematuria are listed in Table 3.
Table 1. Differential Diagnosis for Hematuria

Site
Conditions
Renal
Glomerular
Proliferative glomeru- IgA nephropathy, HSP, postinfectious
lonephritis
glomerulonephritis (strep), membranoproliferative glomerulonephritis, vasculitides (SLE,
Goodpasture syndrome, ANCApositive vasculitis [microscopic
polyangitis, Wegener granulomatosis, Churg-Strauss syndrome],
scleroderma, cryoglobulinemia)
Nonproliferative
Minimal change disease, focal
glomerulonephropsegmental glomerulosclerosis,
athies
membranous nephropathy, HUS/TTP
Familial
Alport syndrome, Fabry disease,
thin basement membrane nephropathy (or benign familial hematuria)
Others
Renal allograft rejection, postradiotherapy
Nonglomerular
Neoplasms
Renal cell & transitional cell
carcinoma, simple renal cysts
Familial
Polycystic kidney disease, medullary
sponge kidney
Vascular
Renal infarction (thrombotic,
embolic), renal vein thrombosis,
aneurysms, arteriovenous malformation, arteriovenous fistula
Infectious
Pyelonephritis, xanthogranulomatous
pyelonephritis, TB, Cryptococcus
Metabolic
Hypercalciuria, hyperoxaluria
159
Table 1 (continued)
Site
Nonglomerular (continued)
Trauma
Others
Lower urinary tract

Ureteral
Bladder
Urethral
Prostatic
Others
Hematologic
Drug/toxin
Miscellaneous
False-positives
Conditions
Laceration, contusion, stones

Acute interstitial nephritis, loin
painhematuria syndrome,
malignant hypertension, papillary
necrosis
Stones, trauma, transitional cell
carcinoma
Cystitis (also interstitial vs.
postradiotherapy), transitional cell &
papillary carcinoma, rapid emptying
of distended bladder, Schistosoma
haematobium, stones, trigonitis,
post-cystoscopy, enterovesical
fistula
Urethritis, meatal stenosis, caruncle,
stricture, prolapse, foreign body,
trauma from Foley catheter,
urethral neoplasm, stones
BPH, prostatitis, prostatic adenocarcinoma, post-prostatectomy
Over anticoagulation, anticoagulation
unmasking genitourinary lesion,
thrombocytopenia, hemophilia,
bleeding diathesis, sickle cell
Cyclophosphamide (hemorrhagic
cystitis), NSAID, phenacetin
Vulvovaginitis, menstruation,
endometriosis, vaginal foreign body,
sexual abuse, anal fissure, vigorous
exercise (runners), factitious
Myoglobinuria, hemoglobinuria,
food coloring, rifampin, beetroot
ANCA, antineutrophil cytoplasmic antibody; BPH, benign prostatic hypertrophy; HSP, Henoch-Schnlein purpura; HUS, hemolytic uremic syndrome;
SLE, systemic lupus erythematosus; TTP, thrombotic thrombocytopenic
purpura.
160
I SIGNS & SYMPTOMS

Characteristics of Hematuria
Glomerular or renalbrown or cola-colored urine, dysmorphic red cells (>25%), red cell casts
Extrarenalgross hematuria with complete clearing between;
pink or red urine; more likely to clot
Urethral sourcehematuria at initiation of stream
Prostatic or bladder neck sourcehematuria present in last
few drops of urine
Bladder, ureteral, or renal sourcehematuria present throughout stream
Gynecologic sourcecyclical through the month (vaginal
bleeding with menses), endometriosis of bladder or urethra
Urinalysis
Glomerular hematuriaRBC casts, dysmorphic RBCs, proteinuria (gross hematuria alone may be responsible for up to
500 mg protein/24 hours)
Nonglomerular hematuriaclotting, rounded RBCs
Table 2. Common Causes of Hematuria by Age

Age, y
Causes (in descending order)
<20
UTIs
Glomerulonephritides
Congenital tract anomalies
UTIs
Stones
Carcinoma (bladder/kidney)
UTIs
Stones
UTIs
BPH
Systemic vasculitis
20-40
40-60
>60
BPH, benign prostatic hypertrophy; UTI, urinary tract infection.

161
162
Table 3. Causes of Hematuria, Clinical Presentation, and Lab Findings

Cause
Urinary tract infection,
pyelonephritis
Stones
Poststreptococcal
glomerulonephritis
IgA nephropathy
Prostatitis
Benign prostatic
hypertrophy
History
Physical exam
Test
Frequency, dysuria
Fever, CVA tenderness
Positive urinalysis Gram stain
Colicky flank pain radiates to groin,

frequent in Asian children (calcium
oxalate), family history
Pharyngitis (latency, 7-10 days), skin
infection (latency, 21-30 days), brown
or cola-colored urine, oliguria
Most common type of glomerulonephritis in children
Hematuria (microscopic or macroscopic), proteinuria after URI or
exercise
Most common cause of hematuria in
world (30%)
Perineal pain, terminal hematuria in
males
Hesitancy, weak stream, dribbling
Orthostatism, CVA
tenderness
80% seen on KUB, may need

spiral CT
HTN, edema, fever, residual

pharyngitis, healing
pyoderma
Low levels of complement,

positive ASO titer, dysmorphic
RBCs in urine, RBC casts
Normal, may have

HTN/edema
Renal biopsy
Boggy tender prostate
WBCs in urinalysis
Enlarged, soft, smooth

prostate
Mildly elevated prostate-specific

antigen
Table 3 (continued)
Cause
Papillary necrosis
Renal artery embolism/

thrombosis
Renal laceration or
trauma
Urethral injury
163
Malignant HTN
Headaches, visual changes, TIA-like

symptoms
Bleeding dyscrasia
Family history, ethnicity, abnormal

coagulation, bleeding, bruising
Physical exam
Test
Elevated hemoglobin A1c,

sickle cell screen, urine
acid-fast bacteria
HTN, irregular pulse, new Doppler study, angiography
murmurs, flank bruits,
livedo reticularis
May correspond to
predisposing cause
Orthostatism
Doppler study, angiography
Hypotension, flank
ecchymosis
High-riding, ballotable
prostate; perineal
ecchymosis; urethral
blood
HTN, fundus arteriovenous nicking, exudates/
hemorrhage, S4
Pallor, ecchymosis, joint
deformities
CT abdomen
Pelvic X-rays, retrograde
urethrography
ECG, CT head, urinalysis,

creatinine
Special coagulation studies,
hemoglobin electrophoresis
I SIGNS & SYMPTOMS
History
Diabetes mellitus, sickle cell anemia,
analgesics, TB, ethanol, ankylosing
spondylosis, obstructive uropathy
Recent angiogram or myocardial
infarction, palpitations or pulse
irregularity, subacute bacterial
endocarditis
History of nephrotic syndrome or paroxysmal nocturnal hemoglobinuria
History of motor vehicle accident,
blunt trauma to abdomen, back
History of motor vehicle accident,
pelvic fracture
164
Table 3 (continued)
Cause
Sickle cell anemia
ANCA-positive
vasculitis
HUS/TTP
Henoch-Schnlein
purpura
Alport syndrome
History
Males>females, source from left>right
kidney, associated with papillary
necrosis, glomerulopathy, bacteria,
hyperuricemia, incomplete renal
tubular acidosis, nephrogenic
diabetes insipidus
Paresthesias, arthralgias, skin lesions,
abdominal pain, anemia, hematuria,
proteinuria, sinusitis, epistaxis
Prodrome of bloody diarrhea
Physical exam
Test
Orthostatism, pallor, pain
Sickle cell screen
Neuropathies, skin rash,

purpura, others
ANCA testing (anti-MPO, antiPR3) biopsy
Pallor, ecchymosis, fever,

Peripheral blood smear, stool
mental status changes
culture, creatinine
Need to exclude other causes
Usually boys 2-11 years old, arthralgias, Non-thrombocytopenic
crampy abdominal pain, melena
purpura of lower extremities of purpura
or buttocks, arthritis
Deafness, anterior lenticonus, Clinical diagnosis, may need
High-frequency sensorineural hearing
renal biopsy
loss, family history of end-stage renal
yellow perimacular flecks
failure in 2nd-3rd decade, X-linked,
ocular abnormality, defect 5 chain,
type IV collagen chain
Table 3 (continued)
Cause
History
Goodpasture syndrome
Hemoptysis, hematuria, proteinuria
Scleroderma
Bladder carcinoma
Renal cell carcinoma
Coarse breath sounds,

rales, pallor
Finger changes white to red to blue,
Sclerodactyly, ulcerated
arthritis, dyspnea
fingers, calcifications,
wide split S2 with
loud P2
Females>males, 2nd-3rd decades,
Butterfly rash, arthritis,
fevers, rash, arthritis, Asians>African pulmonary rales or rubs
Americans>whites
Previous pelvic radiotherapy, chemo- Suprapubic mass, pelvic
therapy with cyclophosphamide,
lymphadenopathy
smoking; work in textile, metal,
rubber, paint, or printing industry
Smoking; work in tannery, asbestos,
Fever, flank mass, leftcadmium, lead acetate, or petroleum
sided varicocele
industry; family history of
von Hippel-Lindau disease
Test
anti-GBM, MPO, PR3,
renal biopsy
Anti-centromere &
anti-Scl70
ANA, anti-dsDNA, antihistone (drug-induced)

Cystoscopy with biopsy
CT or MRI
165
I SIGNS & SYMPTOMS
Systemic lupus
erythematosus
Physical exam
166
Table 3 (continued)
Cause
History
Physical exam
Firm, irregular, nodular
prostate
Prostate adenocarcinoma
High fat diet, family history
Exercise-induced
Transient 24-48 hours after exertion,

Normal
distance runners, 15%-20% of normal
persons
History of pelvic surgery or radiotherapy Fecaluria, pneumaturia
Enterovesicular fistula
Test
Transrectal ultrasonography with
biopsy, elevated prostate-specific
antigen
Urine normalizes
Urinalysis with polyenteric

organisms
ANCA, antineutrophil cytoplasmic antibody; ANA, antinuclear antibody; ASO, antistreptolysin O; CVA, costovertebral angle; dsDNA, double-stranded DNA; GBM,
glomerular basement membrane; HTN, hypertension; HUS, hemolytic uremic syndrome; KUB, kidney, ureter, bladder; MPO, myeloperoxidase; P2, 2nd pulmonic
sound; PR3, proteinase 3; S2, 2nd heart sound; S4, 4th heart sound; TIA, transient ischemic attack; TPP, thrombotic thrombocytopenic purpura; URI, upper respiratory tract infection.
I SIGNS & SYMPTOMS

An algorithm for evaluating hematuria is provided in
Figure 1.
INITIAL MANAGEMENT
Urinary tract infection or pyelonephritis
Urine culture, blood culture if hypotensive (positive in up
to 20%)
Antibiotics
IV if unable to take PO, pregnant, or unstable
(quinolones, 3rd-generation cephalosporins)
Oral antibiotics when stable (trimethoprimsulfamethoxazole, quinolones)
Treat for 3-5 days for cystitis and 10-14 days for
pyelonephritis
Calculi
Aggressive IV hydration, pain control (may need morphine patient-controlled analgesia)
Strain urine for stone analysis.
24-Hour urine for calcium, phosphorus, urate, cystine,
citrate, oxalate, creatinine, sodium, potassium
Urology consult for large stones (>4 mm) in need of extracorporeal shock wave lithotripsy
Bladder carcinoma
Urology consult
Staging
CT of chest, abdomen, and pelvis to evaluate spread
and metastasis
Liver function tests, bone scan
Proctoscopy to rule out rectal involvement if invasive
Preoperative medical evaluation
Renal cell carcinoma
Urology consult
Staging
Creatinine clearance, liver function tests, calcium, bone
scan
CT of chest, abdomen, and pelvis to evaluate spread
and metastasis
167
MRI to evaluate for renal vein and inferior vena cava

tumor thrombus
Benign prostatic hypertrophy
Bladder scan to rule out retention
Lab tests
Creatinine
Prostate-specific antigen, if baseline available to compare, to rule out malignancy (do not draw blood sample
after Foley placement or aggressive digital rectal exam
because these cause false-positive results)
May begin tamsulosin, 0.4 mg PO daily
If obstruction, consult urology to consider transurethral
resection of prostate
Glomerulonephritis
Lab testsC3, C4, CH50, ASO, ESR, ANA, ENA panel,
ANCA (anti-MPO, anti-GBM), cryoglobulins, creatinine,
serum protein electrophoresis
Urine studieseosinophils, hemosiderin, myoglobin, 24hour urine creatinine and protein, urinary immunoelectrophoresis
Chest X-ray
Nephrology consult
Anticoagulation
Discontinue anticoagulation if INR/aPTT supratherapeutic
May need vitamin K or fresh frozen plasma to reverse
warfarin or protamine sulfate to reverse heparin if bleeding is severe
If anticoagulation is essential but limited by bleeding, fully
reverse the warfarin and titrate heparin as bleeding allows.
Bleeding while therapeutic on anticoagulation, requires
same work-up as above given likelihood of disease (80%
of the time if therapeutically anticoagulated)
168
I SIGNS & SYMPTOMS

Positive dipstick
UA with RBCs
No
Myoglobinuria, hemoglobinuria
Yes
UA with WBCs
Yes
Culture urine, antibiotics prn

Check urine eosinophils
No
Dysmorphic RBCs,
RBC casts,
proteinuria (>500
mg/day)
No
Renal US/CT
urogram (with and
without contrast)
Sickle cell screen
positive urine
cytology and/or
FISH test
Negative
Yes
Renal US, C3, C4, CH50, ANA, ENA

panel, anti-GBM, ANCA panel,
ESR, C-reactive protein, cryoglobulins, ASO, hepatitis B & C, HIV
And
Nephrology consult
Consider renal biopsy
Negative
Cystoscopy with
retrograde
pyelograms
Fig. 1. Algorithm for hematuria evaluation. ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody; ASO, antistreptolysin O; ENA, extractable nuclear antigen; FISH, fluorescence in
situ hybridization; GBM, glomerular basement membrane; IVP, intravenous pyelography; MPO, myeloperoxidase; prn, as needed; UA,
urinalysis; US, ultrasonography.
169
I SIGNS & SYMPTOMS

HEMOPTYSIS
Otis B. Rickman, D.O.
Udaya B. S. Prakash, M.D.

Hemoptysis
Definitionexpectoration of blood from respiratory tract
Common respiratory symptom (patient complains about it
before it is seen)
Most commonly due to bronchitis
Frequently portends an ominous diagnosis
Expedient evaluation is required.
Massive hemoptysislife-threatening!
Definition (arbitrary)200 mL blood expectorated in
24 hours
Occurs in 1%-4% of patients with hemoptysis
Deathusually caused by asphyxiation, occasionally by
exsanguination
Look for signs of respiratory failure or hemodynamic
collapse
Lung blood supply
Dual supplylow-pressure pulmonary artery and highpressure bronchial arteries
Bronchial artery90% of cases of hemoptysis
Can die of hemoptysis of low-pressure side (Rasmussen
aneurysm)
ADDRESSING THE RISK
Airway, breathing, circulation, and differential
Evaluate and manage concurrently.
If patient is actively bleeding, high operative mortality; thus,
stop the bleeding.
Surgeryonly for a good operative candidate with localized bleeding
High-resolution CT and bronchoscopy are complementary
171
Hemoptysis is a symptom with a broad differential diagnosis (Table 1).
Mnemonic devicevery fast docs pitch in (vascular, factitious, drugs/toxins, other, cavitary, systemic disease, pulmonary, iatrogenic, trauma, cardiac, hematologic, infection,
neoplastic) (Table 1)
Diagnoses suspected on the basis of the history and physical
exam findings are listed in Table 2.

For every patient with hemoptysischest X-ray, CBC, type
and screen, and arterial blood gases
Also, sputum with Gram stain, culture, acid-fast bacteria,
and cytology if clinically indicated
Depending on what is suspectedhigh-resolution CT, ventilation-perfusion scan, echocardiography, bronchoscopy
(Fig. 1)
INITIAL MANAGEMENT
The algorithm in Figure 1 includes a strategy for managing
hemoptysis.
172
I SIGNS & SYMPTOMS

Table 1. Differential Diagnosis for Hemoptysis
Vascular
Pulmonary embolism (clot,
tumor, fat, septic)
Pulmonary hypertension
Aneurysm
Leaking graft
Factitious
Drugs/toxins
Aspirin
Warfarin/heparin
Nitrofurantoin
Penicillamine
Solvents
Other
Catamenial
Broncholithiasis
Foreign body
Lymphangioleiomyomatosis
Cryptogenic
Cavitary
TB
Mycetoma
Abscess
Bronchogenic cancer
Wegener granulomatosis
Sarcoidosis
Systemic disease/diffuse
alveolar hemorrhage
Goodpasture syndrome
Microscopic polyangiitis/
polyarteritis nodosa
Churg-Strauss syndrome
Systemic lupus erythematosus
Behet syndrome
Idiopathic pulmonary
hemosiderosis
Pulmonary
Bronchitis
Bronchiectasis
Cystic fibrosis
Iatrogenic
Pulmonary artery catheter
Transthoracic biopsy
Bronchoscopy
Trauma
Puncture
Laceration
Contusion
Bronchial disruption
Cardiac
Mitral stenosis
Congenital heart disease
Hematologic
Thrombocytopenia
Platelet dysfunction
Coagulopathy
Uremia
coagulation
Infection
Bronchitis
Pneumonia (bacterial,
fungal, viral)
Abscess
TB
Parasites
Neoplastic
Squamous cell
Adenocarcinoma
Carcinoid
Endobronchial adenoma
Metastases
173
Table 2. Diagnosis Suggested by History and Physical

Exam
History and physical
exam clues
Suspected
diagnosis
Fever, blood-streaked
mucopurulent sputum,
normal chest X-ray,
seasonal
Large-volume, purulent sputum; history
of severe infection
or TB
Fever, rigors, adventitious sounds, consolidation, infiltrate
on chest X-ray
Chronic aspiration
(alcoholic, dysphagia,
seizures), poor
dentition
Positive PPD, exposure,
previous history of/risk
factors for TB
Neutropenic, immunocompromised
Past history of cavitary
disease, now fever
& chills
Smoker, weight loss,
>40 years old
Acute bronchitis
None
Bronchiectasis
High-resolution CT
Pneumonia
Sputum & blood

cultures
Lung abscess
CT chest
TB
Sputum acid-fast
bacteria, PPD,
chest X-ray
Biopsy
Pleuritic chest pain,

dyspnea, immobility,
pleural rub, deep
venous thrombosis
Recent bronchoscopy,
lung biopsy, pulmonary artery catheter
Status post thoracic
aneurysm repair
Hematuria
Pneumothorax, effusion,
child-bearing age
female
174
Invasive aspergillosis
Mycetoma
Bronchogenic
cancer
Further testing
Chest X-ray or
CT chest
Pulmonary
embolism
Sputum cytology,
flexible fiberoptic
bronchoscopy
Spiral CT or V/Q
scan
Trauma
See Figure 1
Fistula
Aortography
Vasculitis
Lymphangioleiomyomatosis
Anti-GBM, ANCA
Thoracentesis,
high-resolution
CT
I SIGNS & SYMPTOMS

Table 2 (continued)
History and physical
exam clues
Suspected
diagnosis
Cyclic hemoptysis
occurring with menses
S3, edema, elevated
jugular venous
pressure
Opening snap, diastolic
murmur
Telangiectasias, bruit
over chest
Catamenial
hemoptysis
Congestive heart
failure
Mitral stenosis
Further testing
Suppress menses
Echocardiography
Echocardiography
Osler-Weber-Rendu Family history

disease
ANCA, antineutrophil cytoplasmic antibody; GBM, glomerular basement

membrane; S3, 3rd heart sound; V/Q, ventilation-perfusion.
175
176
History & physical exam
Fig. 1. Algorithm for ordering diagnostic tests and managing hemoptysis.

ABG, arterial blood gases; AFB, acidfast bacillus; Echo, echocardiography;
ET, endotracheal; FEV1, forced expiratory volume in 1 second; FFOB, flexible fiberoptic bronchoscopy; PAVM,
pulmonary arteriovenous malformation;
V/Q, ventilation-perfusion.
Intubation indications
Hypoxia
Hypercarbia
Impending shock
Massive bleeding
Obtundation
Surgery
Indications
Unilateral disease
Failure of medical therapy
Contraindications
Terminal disease
Baseline hypoxia
Baseline hypercarbia
Dyspnea at rest
Predicted postop FEV1 <800
Lung origin
pH >7.5, frothy, bright
red, mixed with sputum
Thrombocytopenia
CBC, PTT/INR, ABG,
type & screen, chemistry
panel, urinalysis, chest
X-ray, sputum (Gram
stain culture, AFB,
cytology)
Bleeding side-dependent
Replace
Replace
Uremia
Desmopressin
Infectious
Antibiotics
Positive cytology
Bronchoscopy
Pulmonary consult
Milliliters of blood
<200 mL/24 hours

Volume resuscitation
Appropriate
evaluation
Coagulopathy
Two large-bore
antecubital IVs
_>200 mL/24 hours

Transfer to ICU
Gastrointestinal
Ear-nose-throat
Chest X-ray
Secure airway
Abnormal
Normal
Notify
Bronchoscopist
Thoracic surgeon
Invasive radiologist
FFOB
Embolization
Supportive or
specfic therapy
Malignancy
Peripheral
Diffuse bleeding
Balloon tamponade
Iced saline
Vasoconstrictors
Topical coagulants
High-resolution CT
Normal
V/Q scan
Echo
CT-guided biopsy
Emergent surgery
Cryptogenic
177
Fig. 1 continued
Low
Bronchiectasis
Cavity PAVM Vascular Infectious
Specific therapy
I SIGNS & SYMPTOMS
Localized bleeding
Selective intubation
Dual-lumen ET tube
High
Central
Early FFOB
Malignancy risk factors

Male
>40 years old
40-pack-year history
Suspicion for
malignancy
I SIGNS & SYMPTOMS

HEPATOMEGALY
Santhi Swaroop Vege, M.D.

The most life-threatening conditions that must be ruled out
immediately include
Fulminant hepatic failure (most cases may not have
hepatomegaly because of marked hepatic necrosis and
shrinkage of the liver)
Closed abdominal trauma with liver or splenic rupture
Acute hepatic vein thrombosis
Sepsis
Hepatic infarction
Severe biliary obstruction
The following features are suggestive of the above:
Acute onset of symptoms (<10 weeks)
History of toxic ingestion (drugs such as acetaminophen)
Fever
Hypotension
Early signs of encephalopathy (changes in sleep-wake
cycle, agitation-anxiety, personality change, altered mental status)
Hypoglycemia
PT >3 seconds
Bilirubin >20 mg/dL
Acute abdominal pain and distension
Signs of peritonitis
ADDRESSING THE RISK
If any of the above conditions is suspected, proceed as follows:
Special abbreviations used in this chapter: ERCP, endoscopic retrograde cholangiopancreatography; HAV, hepatitis A virus; HBc, hepatitis B core; HBsAg,
hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus.
179
Obtain good intravenous access and start IV fluids.

Give nasal oxygen.
Start empiric treatment with antibiotics (piperacillin-tazobactam) after blood cultures if sepsis or trauma is suspected.
Start acetylcysteine immediately if acetaminophen ingestion is suspected.
Call ICU immediately.
Contact liver transplant service for fulminant hepatic failurethe sooner the better.
Obtain as a priority
Bilirubin, ALT, AST, alkaline phosphatase, PT, albumin, hepatitis viral serologic studies (IgM anti-HAV,
IgM anti-HBc, HBsAg, and anti-HCV), blood gases,
blood cultures, acetaminophen level
Abdominal ultrasound with Doppler study of venous
and/or arterial system
The causes of hepatomegaly may be subdivided into the following categories: venous congestion, biliary obstruction,
infectious/inflammatory, infiltrative, cystic liver disease, and
others (Table 1).
Note50% of all cases of hepatomegaly in hospitalized
patients are due to congestive heart failure.

History of Present Illness
Acute vs. chronic disease
The abrupt onset of symptoms suggest an acute liver injury
such as infectious or inflammatory (most likely viral),
toxic, congestive (acute right-sided heart failure)
Characteristics of the symptoms
Confusion, somnolence, agitation, tremulousness: hepatic encephalopathy
Nausea and vomiting: acute liver insult and/or necrosis
Anorexiacommon symptom in acute and chronic liver
disease
Right upper quadrant paininfectious or inflammatory
Increase in abdominal girthsuggestive of ascites,
spontaneous bacterial peritonitis, hepatic malignancy,
venous outflow obstruction
180
I SIGNS & SYMPTOMS

Table 1. Causes of Hepatomegaly
Venous
Tricuspid regurgitation
Constrictive pericarditis
Cor pulmonale
Budd-Chiari syndrome
Veno-occlusive disease (chemotherapy, radiation, bone marrow
transplant, pyrrolizidine alkaloids)
Biliary obstruction
Common duct gallstones
Biliary stricture
Pancreatitis
Neoplasm (pancreatic, biliary, ampullary)
Inflammatory
Infectious
Diffusehepatitis (A, B, or C), CMV, infectious
mononucleosis, herpes simplex, HIV, TB, histoplasmosis,
actinomycosis, brucellosis, schistosomiasis, falciparum
malaria
Localizedpyrogenic abscess, Entamoeba histolytica
Noninfectiousalcohol, toxin- & drug-induced hepatitis,
autoimmune hepatitis, primary biliary cirrhosis, primary
sclerosing cholangitis, Wilson disease, Reye syndrome
Infiltrative
Primary or metastatic cancer
Lymphoma
Nonalcoholic steatohepatitisdiabetes mellitus,
alcohol, hyperalimentation, malnutrition
Amyloidosis
Hemochromatosis
Sarcoidosis
Glycogen storage disease
Alpha1-antitrypsin deficiency
Cystic
Adult polycystic kidney disease
Pyogenic abscess
Entamoeba histolytica
Echinococcus granulosus
Other
Riedel lobe
Nonhepatic mass
CMV, cytomegalovirus.
181
Prurituscholestasis
JaundicePainless jaundice suggests a neoplasm obstructing the bile duct (check for a palpable gallbladder on exam,
Courvoisier law).
Intermittent jaundice, suggests a stone in the bile duct
with cholangitis.
With dark urine and light stoolscholestasis
Without pruritusacute hepatitis (viral- or druginduced)
Hyperpigmentationchronic cholestatic liver disease
(e.g., primary sclerosing cholangitis, primary biliary cirrhosis), hemochromatosis
Ecchymosesadvanced chronic liver disease with/without hypersplenism (may occur with petechiae, gingival
bleeding)
UrticariaHBV or HCV infection (with synovitis),
immune complex disease (with petechiae)
Pharyngitis, rash, and lymphadenopathyEpstein-Barr
virus or cytomegalovirus
Family History
Genetically linked chronic liver diseaseWilson disease,
hemochromatosis, alpha1-antitrypsin deficiency, polycystic
kidney disease, autosomal dominant polycystic liver disease,
autoimmune disease
Hereditary predispositionalcoholic liver disease, drug
abuse
Perinatal exposure to HBV (high prevalence of hepatitis B in
Asia and Africa)
Social History
Household contact with hepatitis A or food contamination
Promiscuous sexual activity, ilicit drug use, history of blood
transfusionviral hepatitis
Exposure to a hepatotoxic medication or environmental toxin,
including ethanol use
Institutional exposurehealth care experience, institutionalized or imprisoned (viral hepatitis)
Oral contraceptiveshepatic vein thrombosis, cholestasis,
hepatic adenoma
182
I SIGNS & SYMPTOMS

Physical Exam
General
Cushingoid features (chronic corticosteroid treatment of
liver disease, autoimmune chronic active hepatitis) and
signs of chronic liver disease
Cachexiamalnutrition (ethanol), malignancy
Head
Scleral icterusjaundice
Kayser-Fleischer ringsWilson disease
Dry eyes/mouth (sicca syndrome/autoimmune disease,
primary biliary cirrhosis), buccal icterus (jaundice)
Neck
Adenopathylymphoproliferative or metastatic disease,
viral hepatitis, granulomatous disease
Distended neck veins and hepatojugular reflexcongestive heart failure
Kussmaul sign (elevated jugular venous pressure with a
paradoxical elevation during inspiration)constrictive
pericarditis or tamponade
Chest
Gynecomastia, spider angiomaschronic liver disease,
usually ethanol
Chest hyperresonance (emphysema)alpha -antitrypsin
1
deficiency
Cardiac
Third heart sound gallopcongestive heart failure
Cardiomegaly (displaced apical impulse)congestive
heart failure, alcoholism, hemochromatosis, or amyloidosis
Right ventricular heaveright ventricular failure, pulmonary hypertension, cor pulmonale
Increased second pulmonic soundpulmonary hypertension
Holosystolic murmur that increases with inspirationtricuspid regurgitationpulmonary hypertension, cor pulmonale, advanced congestive heart failure
Constrictive pericarditisdiastolic pericardial knock,
widening of the split between the aortic and pulmonic
183
components of the second heart sound may occur, a friction

rub is best heard using the diaphragm of the stethoscope
at the left lower sternal border. The friction rub is easier
to hear if respirations are suspended.
Abdomen
Liver
Displaced liver/benign hepatomegalyincreased
height and weight, hyperinflated lungs, Riedel lobe,
males
Tendernessacute, infectious, or inflammatory causes more likely
Nodularitytumor, polycystic disease, macronodular
cirrhosis
Pulsationincreases with inspiration (tricuspid regurgitation), decreases with inspiration (constrictive
pericarditis)
Friction rubinflammation, recent trauma (liver biopsy), malignancy (surface implants), gonococcal
perihepatitis
Bruitsvascular tumor, arteriovenous fistula, acute
alcoholic hepatitis
Venous humsevere tricuspid regurgitation, severe congestion, collateral blood flow from portal hypertension
Splenomegalyportal hypertension
Caput medusaecollateral blood flow from portal
hypertension
Extremities
Edemacongestive heart failure, cirrhosis
Clubbing of fingers and toesarteriovenous fistula, congenital cyanotic heart disease, chronic liver disease (hepatitis C)
Dupuytren contracturesethanol abuse
Nervous system
Disorientation, tremor, asterixisencephalopathy
Cerebellar dysfunction, gross tremor (particularly in wingbeating position), slurred speech, hypertonicityethanol
abuse, Wilson disease

An algorithm for examining a patient who has hepatomegaly
is presented in Figure 1.
184
Hepatomegaly
Cardiac exam
Normal
Abnormal
CHF
Tricuspid regurgitation
Cor pulmonale
Order the following studies: bilirubin,

ALT, AST, AP, PT, albumin
AST, ALT < 300 U/L
AST, ALT > 500 U/L
Acute or chronic hepatocellular injury,

infiltrative diseases, CHF, biliary
obstruction, muscle injury
Cholestasis, common duct stones, biliary strictures

(e.g., PSC, cholangiosarcoma), pancreatitis,
neoplasm (pancreatic or ampullary cancer)
Normal
Riedel lobe, hyperinflated lungs,
depressed right diaphragm
Ultrasound, CT with IV contrast
Ultrasound, CT with IV contrast
Abnormal
Diffuse lesions/abnormality
185
Inflammatory/infiltrative process
Neoplasm (metastatic, lymphoma,
multifocal hepatoma)
Venous congestion
Cirrhosis
Polycystic disease
Focal lesions
Dilated bile ducts, common duct stones
Tumor (primary or metastatic)

Abscess (pyogenic, Entamoeba
histolytica, Echinococcus
granulosis)
Polycystic disease
Macronodular cirrhosis
Proceed to treat the condition
Fig. 1. Algorithm for examining a patient who has

hepatomegaly. AP, acid phosphatase; CHF, congestive
heart failure; PSC, primary sclerosing cholangitis.
I SIGNS & SYMPTOMS
Acute hepatocellular injury (viral-,

drug-, or toxin-induced, ischemic)
Increase in AP, bilirubin modest increase in AST/ALT
If there is ascites, always obtain a diagnostic sample for

Serum-ascitic fluid albumin gradient: >1.1 = cirrhosisrelated causes (97% specificity)
Cytology
CBC and differential: >250 neutrophils = spontaneous
bacterial peritonitis
Amylase: >1,000 mg/dL = pancreatic ascites
Gram stain and cultures
INITIAL MANAGEMENT
Venous Congestion
Congestive heart failurelow salt diet, diuretics, spironolactone, digoxin, -blockers, angiotensin-converting enzyme
inhibitors
Suprahepatic vein thrombosis (Budd-Chiari syndrome)thrombolysis, anticoagulation, surgical shunt, and liver transplant
Biliary Obstruction
Common bile duct gallstonesendoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy
Biliary stricture
Cholangitisblood cultures, CBC, and IV piperacillintazobactam
ERCPdiagnosis, biopsy, dilation with stent placement
Neoplasmsurgical resection if resectable, otherwise palliative bypass procedure, chemotherapy, radiotherapy
Inflammatory
Ethanol hepatitisabstinence from ethanol, vitamin replacement (folate, thiamine), nutritional support, and corticosteroids if criteria are met: discriminant function (DF) >32
[DF = 4.6 (PT PT control ) + bilirubin] or presence of
encephalopathy
Viral hepatitisOrder hepatitis serology tests; give supportive care treatment, with the patient avoiding strenuous
exertion, ethanol, and hepatotoxic agents.
Hepatitis Aimmune globulin is given to all close personal
contacts.
Hepatitis Bimmune globulin is effective if given within 7 days of exposure, followed by the vaccination series
for sexual contacts.
186
I SIGNS & SYMPTOMS
Acetaminophen overdoseEmpty the stomach by emesis

or gastric lavage; if 1-2 hours after ingestion, administer
activated charcoal. Begin acetylcysteine at 140 mg/kg PO,
then 70 mg/kg every 4 hours for 17 doses if
History of acetaminophen abuse and lab evidence of
hepatoxicity
Serum acetaminophen concentration is above the possible
hepatic toxicity line of the Rumack-Mathew nomogram
A single ingestion of >7.5 g acetaminophen by history
and results of serum concentration are not available
Serum concentration is >10 g and time of ingestion is
not known
Infiltrative
Nonalcoholic steatohepatitisgradual weight loss, lipid
management, diabetes mellitus control, low fat diet
Ethanol steatohepatitisreversible with discontinuation of
ethanol or treatment of underlying condition
Neoplasm (metastatic>primary)Treatment and management depend on the cause of the tumor and associated
symptoms.
187
I SIGNS & SYMPTOMS

JOINT PAIN
Peter D. Kent, M.D.
Thomas G. Mason, M.D.

First, rule out the possibility of a musculoskeletal emergency.
The presence of a warm, swollen, tender joint mandates
immediate evaluation.
Red flags include
Fever, chills, weight loss, night sweats
Trauma to a limb or joint area
Neurologic compromise
Acute onset of symptoms
Septic arthritis is the most important cause of acute joint
pain to rule out; it is a medical emergency.
ADDRESSING THE RISK
If septic arthritis is a possibility, aspirate synovial fluid from
the involved joint(s).
The following studies should be ordered on synovial fluid:
Culture
Gram stain
Cell count and differential
Crystal analysis
Base the choice of antibiotics for empiric treatment on the
Gram stain results.
X-ray the joint area if trauma is involved or tumor is
suspected.
Inflammatory arthritis may be distinguished from noninflammatory by the following:
Warmth over the joint
Synovitis (boggy, swollen synovial tissue)
Pronounced morning stiffness by history
189
Joint effusions may be present in both inflammatory and

noninflammatory arthritis.
Arthralgias without arthritis
Viral illness
Subacute bacterial endocarditis
Fibromyalgia
Bursitis
Tendinitis
Fasciitis
Metabolic bone disease (osteomalacia, hyperparathyroidism)
Soft tissue injury
Neuropathy

Is There a History of Trauma or Focal Bone Pain?
If so, obtain an X-ray, with at least two views at 90 angles
from each other.
If film is abnormal, the possibilities include fracture, tumor,
or metabolic bone disease.
Is the Joint Pain Articular or Periarticular?
Articular (joint) pain
Similar with passive and active range of motion
Swelling over the joint
Tenderness along the joint margin
Focuses diagnostic evaluation on the joint(s)
Periarticular pain
Markedly less severe with passive than active movement
Often maximal at beginning of task and improves with
activity
Aggravated with resisted movement or stretch
Site of tenderness may extend perpendicular to joint line
Suggests a diagnosis such as bursitis or tendinitis
Is an Inflammatory Arthritis or Effusion Present?

Look for boggy synovitis or a bulge sign (knee joint).
Ask about morning stiffness, which typically lasts for more
than 1 hour in inflammatory arthritis.
Perform arthrocentesis if not contraindicated.
Inflammatory fluid (>2,000 WBCs/L with >75% PMNs)
suggests crystalline, infectious, or systemic rheumatic disease.
190
I SIGNS & SYMPTOMS
Fluid from a septic joint usually has >50,000 (50 109/L)

WBCs/L.
Noninflammatory fluid suggests osteoarthritis, soft tissue
injury, or viral infection.
Marrow elements in the fluid suggest intra-articular fracture.
Bloody effusions occur with coagulopathy, pseudogout,
tumor, trauma, or Charcot joints
Is Monoarticular or Polyarticular Arthritis Present?

The differential diagnostic possibilities are different for the
two conditions (Tables 1 and 2)
What Is the Time Course?

Acute monarthritis, in which symptoms become maximal
within 12-24 hours, is likely to result from trauma, an infectious process, or crystal-induced synovitis.
Polyarthritis that progresses with a subacute course (few
weeks) occurs with viral arthritis, spondyloarthropathy, and
rheumatoid arthritis.
More insidious and chronic disorders include osteoarthritis
and fibromyalgia.
What Is the Distribution of the Arthritis?

Symmetric involvement of the metacarpophalangeal joints
and proximal interphalangeal joints is characteristic of
Table 1. Differential Diagnosis for Inflammatory and

Noninflammatory Monarthritis
Inflammatory
Infection: viral, bacterial, fungal,
mycobacterial
Crystalline: gout, pseudogout
Other: psoriatic, reactive,
rheumatoid, systemic lupus
erythematosus
Noninflammatory
Fracture or internal
derangement
Osteoarthritis
Other: tumor, hemarthrosis,
amyloidosis
191
Table 2. Differential Diagnosis for Inflammatory and

Noninflammatory Polyarthritis
Inflammatory
Infection: parvovirus, HIV, rubella,
gonococcal, Lyme disease,
Whipple disease, endocarditis
Systemic inflammatory arthritis:
rheumatoid arthritis, systemic
lupus erythematosus, Still
disease, Behet syndrome,
relapsing polychondritis, familial
Mediterranean fever, other
Seronegative spondyloarthropathy:
Reiter syndrome, psoriatic, ankylosing spondylitis, inflammatory
bowel disease
Reactive arthritis: enteric or
urogenital infection, rheumatic
fever
Polyarticular crystalline
Sarcoidosis
Malignancy
Noninflammatory
Osteoarthritis
Hematologic: amyloidosis,
leukemia, hemophilia,
sickle cell disease
Hypertrophic pulmonary
osteoarthropathy
Distal interphalangeal joint involvement occurs in osteoarthritis, Reiter syndrome, and psoriatic arthritis.
Gout has a predilection for the first metatarsophalangeal
joint (podagra) and the ankle.
Pseudogout usually involves the knees and wrists.
Migratory polyarthritis occurs in gonococcal arthritis, viral
infections, sarcoidosis, rheumatic fever, endocarditis, and
systemic lupus erythematosus.
Oligoarthritis with axial involvement occurs in spondyloarthropathies.

The tests ordered according to signs, symptoms, and findings
are summarized in Table 3.
ESR and C-reactive protein
Sensitive but not specific
Can be used as a marker of disease activity
192
I SIGNS & SYMPTOMS
Rheumatoid factor
Useful in confirming the diagnosis and assessing prognosis for patients with inflammatory polyarthritis
Frequently false-positive result
Antinuclear antibody
Frequently false-positive result
Extractable nuclear antigens
These should only be ordered if the clinical suspicion is
high for systemic lupus erythematosus, Sjgren syndrome,
scleroderma, or mixed connective tissue disease.
Other tests
Lyme, parvovirus, rubella, and HIV serologic tests are
useful only when clinical suspicion is strong.
Table 3. Summary of Tests Ordered According to Signs,

Symptoms, and Findings
Signs, symptoms,
findings
Diagnosis
Tests ordered
Trauma, focal bone

pain, ecchymosis
Fracture, dislocation, X-ray of affected

tumor, metabolic
joint area
bone disease
Effusion or synovitis Trauma, crystalline
Joint aspiration &
arthropathy,
synovial fluid
infection, systemic
analysis for Gram
rheumatic disease,
stain, CBC, culture,
sarcoidosis, sponcrystal exam with
dyloarthropathy,
polarized light
hemarthrosis, tumor microscope
Urethritis, cervicitis, Gonococcal arthritis Cultures of blood,
migratory arthritis,
skin lesions, synotenosynovitis,
vial fluid, cervix,
vesiculopustular
urethra, pharynx, and
lesions
rectum for Neisseria
gonorrhoeae inoculated at bedside on
Thayer-Martin
medium
193
Table 3 (continued)
Signs, symptoms,
findings
Podagra
Diagnosis
Gout >> pseudogout
Tests ordered
Polarized light
microscopy of
synovial fluid
Uric acid crystals are
needle-shaped, negatively birefringent
Antistreptolysin O
titer, throat culture
Erythema margina- Rheumatic fever

tum, new murmur,
chorea, subcutaneous nodules,
polyarthritis, recent
pharyngitis
Axial arthritis
Ankylosing spondy- Consider lumbosacral
litis, psoriatic
X-ray with sacroiliac
arthritis, Reiter syn- views
drome, inflammatory
bowel disease
Risk factors or
HIV arthritis
HIV serology
clinical findings
suggestive of
HIV/AIDS
Enthesitis, keratoReiter syndrome
Consider serology
derma blennorrhagitests for
cum, urethritis,
Campylobacter,
balanitis, oral ulcers,
Chlamydia,
iritis, conjunctiviSalmonella, Shigella,
tis, history of STD
Ureaplasma, &
or gastroenteritis
Yersinia
Chondrocalcinosis
Pseudogout
Calcium, phosphate,
& arthritis affecting
iron studies, &
knees, wrists,
TSH (to rule out
elbows, & ankles
secondary causes)
CPPD crystals are
rhomboid-shaped,
positively birefringent with polarized
light microscopy
Arthritis, erythema Sarcoidosis or other ACE level, biopsy to
nodosum, hilar
granulomatous
check for noncaseadenopathy
disease
ating granulomas
Fever, heart murmur, Endocarditis
Blood cultures
arthritis
194
I SIGNS & SYMPTOMS

Table 3 (continued)
Signs, symptoms,
findings
Diagnosis
High fever, evanescent pink rash,

polyarthritis, sore
throat
Still disease
Polyarthritis, fever,
rash
Viral arthritis
Nail pitting
Arthritis, diarrhea,
constitutional symptoms, neurologic
symptoms, lymphadenopathy, hyperpigmentation
Oral/nasal ulcers,
rash, iritis, photosensitivity, nodules,
Raynaud disease,
sicca symptoms,
morning stiffness,
pericarditis, pleuritis, neurologic
abnormalities
Immunocompromised host
Psoriatic arthritis
Whipple disease
Tick bite, history of

erythema migrans
Tests ordered
Markedly increased
ferritin with absence
of autoantibodies
Hemoglobin, leukocyte count, erythrocyte count
Serologic tests (parvovirus, hepatitis,
rubella)
Clinical diagnosis
PCR on joint fluid,
for Whipple disease
small-bowel biopsy
Systemic rheumatic
disease
CBC, ESR, rheumatoid factor, synovial

fluid analysis, ANA,
ENA, hepatitis,
serologic tests
Fungal or mycobacterial arthritis
Fungal & mycobacterial cultures on

synovial fluid
Lyme serologic test
Lyme arthritis
ACE, angiotensin-converting enzyme; ANA, antinuclear antibody; CPPD,

calcium pyrophosphate dihydrate; ENA, extractable nuclear antigens; PCR,
polymerase chain reaction; STD, sexually transmitted disease; TSH, thyroidstimulating hormone.
195
INITIAL MANAGEMENT
Fracture
Assess neurovascular status.
Stabilize
X-ray
Septic arthritis
Perform blood and urine cultures.
Staphylococcus aureus is the most common cause of nongonococcal bacterial arthritis.
Start empiric antibiotic therapy based on Gram stain and
clinical scenario.
If Gram stain shows gram-negative organisms, start
ceftriaxone or cefotaxime.
If Gram stain shows gram-positive cocci, start nafcillin.
If Gram stain is negative, both ceftriaxone and nafcillin
are reasonable.
For gonococcal infection, start ceftriaxone and treat coexistent sexually transmitted diseases (chlamydia) with doxycycline or azithromycin.
Consult orthopedic surgeon to consider open debridement
and irrigation.
Lyme disease and Whipple disease require treatment with
special antibiotic regimens.
Gout
Check serum uric acid level (1/3 of patients with acute
gouty attack have normal uric acid level).
NSAIDs are effective in relieving pain and inflammation;
indomethacin is commonly given.
If NSAIDs are contraindicated, intra-articular or parenteral
corticosteroids are useful.
Colchicine may be used to treat acute gout, and it may be
given during the transition to chronic therapy.
In chronic tophaceous gout or multiple attacks, consider
a uricosuric agent (probenecid) or allopurinol, starting 2
months after the current attack resolves.
Uricosurics are not effective if creatinine clearance is
<50 mL/minute.
Uricosurics should not be given if there is a history of
uric acid renal stones or 24-hour urine for uric acid is
>1,000 mg.
Allopurinol requires adjustment for renal function.
196
I SIGNS & SYMPTOMS
Pseudogout (calcium pyrophosphate dihydrate crystal

arthritis)
X-ray to look for chondrocalcinosis
NSAID if not contraindicated
Intra-articular corticosteroid injections (often effective)
Synovial fluid analysis to rule out infection
Check acute phase reactants and rheumatoid factor.
Consider a disease-modifying antirheumatic drug, usually in consultation with a rheumatologist.
Physical therapy to prevent deformity
Seronegative spondyloarthropathies
Sacroiliac X-ray
Physical therapy to prevent deformity
Postinfectious reactive arthritis
If recent enteric or urogenital infection, antibiotics may be
helpful.
Rheumatic fever should be treated with aspirin, penicillin
V potassium to eradicate group A streptococci, and sometimes prednisone.
Hemarthrosis
Evaluate for coagulopathy or thrombocytopenia.
Consider orthopedic evaluation.
Sterile inflammatory arthritis
CBC, ESR, rheumatoid factor, and synovial fluid analysis
Creatinine level, urinalysis
Antinuclear antibody, extractable nuclear antigens, complement levels, plain X-rays
Consider liver function tests and serologic tests for hepatitis B and C, Lyme disease, and parvovirus.
Treatment is based on the underlying cause but may involve
corticosteroids.
Osteoarthritis
NSAID or acetaminophen if not contraindicated
Physical therapy
197
Injection of affected joint with corticosteroid may provide

temporary relief.
Surgery for patients not controlled on medical therapy
Tendinitis and/or bursitis
Consider anesthetic and corticosteroid injection.
Physical therapy
Evaluate for coexistent giant cell arteritis.
Check ESR.
Start prednisone.
Once symptoms have resolved and ESR has returned to
normal, prednisone may be tapered with close monitoring
for symptom recurrence or increasing ESR.
198
I SIGNS & SYMPTOMS

LOWER EXTREMITY PAIN
David H. Pfizenmaier II, M.D., D.P.M.
Thom W. Rooke, M.D.
IS THE PATIENTS LIFE (OR LIMB) AT RISK?

Lower extremity pain can be a manifestation of a local or
systemic process.
The following conditions must be recognized and treated
expeditiously:
Deep venous thrombosis (DVT)
Phlegmasia alba dolens
Phlegmasia cerulea dolens
Acute arterial insufficiency
Compartment syndrome
Vasculitis
Infections
Most other causes of lower extremity pain are nonemergent
and can be diagnosed and treated in due time.
ADDRESSING THE RISK
Inspect the lower extremities, and examine for symmetry,
skin lesions, color changes, edema, and deformity.
Palpate femoral, popliteal, posterior tibial, and dorsalis pedis
arterial pulses. If they are nonpalpable, use portable Doppler
ultrasound to determine whether arterial blood flow is present.
Palpate along muscle groups and joints for tenderness, and
note areas of edema, erythema, and warmth.
Neuromuscular exam
Assess range of motion of all joints, first allowing the
patient to move each joint without assistance.
Note loss of function.
Special abbreviations used in this chapter: ANCA, antineutrophil cytoplasmic antibody; DVT, deep venous thrombosis; HIT, heparin-induced thrombocytopenia;
LMWH, low-molecular-weight heparin; LR, likelihood ratio.
199
Test sensation grossly with light touch and two-point

discrimination.
Check knee (L4) and ankle (S1) reflexes.
Note strength of each muscle group.
Special exam maneuvers
For acute nontraumatic lower extremity pain, the cause
is usually vascular.
Certain exam techniques have traditionally been performed, but the sensitivity and specificity of these findings
are debated and relatively low; therefore, exam findings
must correlate with clinical history.
Subsequent definitive testing is usually warranted.
Homan signpain/tenderness in the calf with forced dorsiflexion of the foot at the ankle. For DVT, sensitivity is
56% and specificity is 39%.
Elevational pallorElevate the lower extremities while
the patient is lying supine. Apply pressure with hands to
milk the feet. Release and examine the amount of time
for color to return to the feet. If pallor persists >30 seconds, patient may have arterial disease.
Venous filling timeAfter evaluating for elevational pallor (i.e., while lower extremities are still elevated), have the
patient move to a sitting position with the lower extremities in a dependent position. Examine the veins on the dorsum of the feet. The amount of time for the first vein to
fill is the venous filling time. Normal is 10-15 seconds.
In arterial insufficiency, venous filling time is delayed
(>30 seconds). In venous valvular disease, venous filling time is usually <10 seconds.
Dependent ruborThis is the amount of rubor (redness)
in the feet 2 minutes after testing venous filling time (i.e.,
patient remains in same position). Pronounced rubor is
usually present in arterial disease.
The differential diagnosis for lower extremity pain is listed
in Table 1.

Vascular
Arterial
200
I SIGNS & SYMPTOMS
Patients may present with symptoms of intermittent claudication or rest pain.

Inspection may show hair loss, muscle atrophy, nail
changes, ulcers, or gangrene.
Exam may show the 6 Ps (pallor, pain, polar/cold,
paresthesia, pulselessness, paralysis), elevational pallor
with dependent rubor, delayed venous filling time.
Table 1. Differential Diagnosis for Lower Extremity Pain

Vascular
Venous
Thrombophlebitis
DVT
Venous stasis
Phlegmasia alba dolens or cerulea dolens
Arterial
Arteriosclerosis obliterans
Thromboangiitis obliterans (Buerger disease)
Arteriovenous fistula
Glomus tumor (hypertrophied arteriovenous anastomosis)
Atheroemboli (cardiac, aortic, cholesterol, post-femoral
artery cardiac catheterization)
Acrocyanosis
Aneurysm
Hematoma
Raynaud disease or phenomenon
Erythromelalgia
Sickle cell disease
Thrombosis (e.g., associated with heparin-induced
thrombocytopenia)
Infectious
Bacterial
Cellulitis
Abscess
Necrotizing fasciitis
Lymphangitis
Gas gangrene
Septic arthritis
Osteomyelitis
TB (arthritis, osteomyelitis)
201
Table 1 (continued)
Spirochetal
Syphilis (osteochondritis, periostitis, polyarthritis)
Lyme disease (angiitis and arthritis, especially the knee)
Viral
Herpes zoster
Arthritis (hepatitis, rubella, human parvovirus B19, HIV)
HIV angiitis
Rickettsialangiitis
Rheumatologic
Skin
Erythema nodosum
Rheumatoid nodule
Scleroderma
Subcutaneouspanniculitis
Synovial
Gout
CPPD/pseudogout
Rheumatoid synovitis
Baker cyst (popliteal synovial cyst)
Bursitis
Muscle
Polymyositis
Dermatomyositis
Inclusion body myositis
Fibromyalgia (fibrositis)
Tendontendinitis
Joint
Infectious (septic)
Connective tissue (systemic lupus erythematosus)
Rheumatoid
Spondyloarthropathies (psoriatic, Reiter syndrome,
enteropathic)
Neuropathic (Charcot joint)
Hemarthrosis (hemophilia, von Willebrand disease)
Hypertrophic osteoarthropathy (periostitis of tubular bones)
Cartilageosteoarthritis
EnthesopathyHLA-B27 spondyloarthropathies (ankylosing
spondylitis, Reiter syndrome, enteropathic [Crohn disease,
ulcerative colitis])
Vasculitic
Polyarteritis (polyarteritis nodosa, microscopic polyangitis)
Behet syndrome
Thromboangiitis obliterans
Leukocytoclastic
Hypersensitivity
Cryoglobulinemia
202
I SIGNS & SYMPTOMS

Table 1 (continued)
Neurologic
Peripheral (for isolated lower extremity)
Radiculopathy
Sciatica
Mononeuritis
Tarsal tunnel syndrome
Neurapraxia
Neuropathy
Reflex sympathetic dystrophy
Musculoskeletal
Muscle
Myalgia
Myositis
Trauma
Cramp
Tendon rupture
Bone
Osteonecrosis (skeletal infarctischemic, aseptic, avascular
necrosis)
Chondritis
Tumor
Periostitis
Neoplastic
Musclesarcoma
Bone
Metastatic lesion (breast, lung, prostate, renal, gastrointestinal, thyroid)
Paget disease (osteitis deformans)
Osteoid osteoma
Osteosarcoma
Ewing tumor
Joint
Carcinomatous polyarthritis
Osteochondroma
Chondrosarcoma
Pigmented villonodular synovitis
Traumatic
Fracture
Frostbite
Burns
Compartment syndrome
CPPD, calcium pyrophosphate dihydrate deposition.
203
Venous
Patients display varicose veins, pitting edema, cyanosis,
brawny hyperpigmentation, induration, stasis dermatitis,
skin ulceration, and lipodermatosclerosis.
In superficial thrombophlebitis, exam may show tenderness, erythema, and a firm cord along an affected vein.
Maneuvers can demonstrate an accelerated venous filling
time (due to incompetent valves).
Infectious
Bacterial
Local signs include erythema, edema, warmth, pain, loss
of function, exudate, subcutaneous crepitus (gas gangrene).
Systemic signs include fever, chills, sweats, nausea, vomiting.
Spirochetal
Bulls eye lesion (erythema chronicum migrans of Lyme
disease)
Maculopapular lesions on palms and soles (syphilis)
Viral
Dermatomal distribution and vesicular lesions (herpes
zoster)
Digital infarction (human parvovirus B19)
Rheumatologic
Examine associated areas of skin involvement, morphology of skin lesions, joint involvement (mono- or polyarticular, symmetric vs. asymmetric) to determine if local or
systemic process.
Neurologic
History and neuromuscular exam (see above)
Musculoskeletal or Traumatic
History and musculoskeletal exam
Neoplastic
History and physical exam

Vascular
For arterial occlusive disease, obtain the ankle-brachial
204
I SIGNS & SYMPTOMS
systolic pressure ratio (ankle-brachial index), which is

abnormal if <0.9.
Segmental systolic blood pressures of the lower extremity
can help locate a stenotic lesion.
Transition from triphasic to biphasic or monophasic
Doppler waveforms in duplex ultrasonography also
suggests the location and extent of stenosis.
Segmental measurements of transcutaneous oxygen levels
can help with determining healing potential and amputation
levels.
Arteriography is the gold standard.
For venous disease, history and physical exam are most helpful.
DVT usually is confirmed by Doppler (duplex) compression ultrasonography, with venography considered the
gold standard.
D-dimer is a highly sensitive assay that leads to many
false-positive results. Thus, D-dimer is most helpful when
it is negative (low) because this likely rules out DVT.
A clinical prediction guide (Table 2) can be used to stratify
patients with suspected DVT into low, moderate, or high
probability groups. A scoring system can be used to
improve the pretest probability of DVT being present by
combining relevant signs and symptoms, risk factors for
DVT, and the presence or absence of an alternative diagnosis (musculoskeletal injury, cellulitis, inguinal
lymphadenopathy). With this stratification, the combination of pretest probability and the results of compression
ultrasonography markedly enhances the reliability of diagnosing DVT.
DVT is reliably diagnosed in patients with high or moderate pretest scores and abnormal compression ultrasonograms (positive LR = infinity and 72, respectively).
Therefore, treatment should be initiated. DVT can be
excluded reliably in patients with low pretest scores and
normal compression ultrasonograms (negative LR =
0.2). All other or discordant groups likely require further
testing (venography or serial compression ultrasonography).
205
Infectious
If infection is suspected, begin with the basics: CBC with differential, blood cultures, and ESR.
For joints, perform diagnostic arthrocentesis and obtain a
plain X-ray.
For bones, the first step is to obtain plain X-rays.
Generally, 3-phase technetium bone scintigraphy is the
next diagnostic test if no superimposed condition
complicates bone remodeling (recent surgery, trauma,
rheumatologic or neoplastic bone disease). In these
situations, adjunctive gallium scans or indium-labeled
leukocytes may be useful in identifying areas of inflammation or infection, respectively.
MRI and CT offer good anatomic resolution and are
excellent adjuncts or alternatives to nuclear imaging
studies.
Table 2. Clinical Measures for Scoring Suspected DVT*
Major points
Active cancer (treatment within previous 6 months or palliative)
Paralysis, paresis, or recent cast immobilization of the lower
extremities
Recently bedridden for >3 days and/or major surgery within
4 weeks
Localized tenderness along distribution of deep venous system
Thigh and leg swelling
Calf swelling that is >3 cm that of asymptomatic leg
(measured 10 cm below the tibial tuberosity)
Strong family history of DVT (>2 first-degree relatives)
Minor points
Pitting edema in symptomatic leg (or greater than
asymptomatic leg)
Dilated (nonvaricose) collateral superficial veins in symptomatic
leg
Recent trauma (60 days in the symptomatic leg)
Hospitalization within previous 6 months
Erythema
DVT, deep venous thrombosis.
*Scoring: High probability if alternative diagnosis not likely and either 1)
3 major points or 2) 2 major and 2 minor points. Low probability if
alternative diagnosis is likely and either 1) 1 major point plus 2 minor
points or 2) 0 major and 3 minor points; also, if an alternative diagnosis is
not likely and 1) 1 major and 1 minor point or 2) 0 major and 2 minor
points. Moderate probability for all other combinations.
206
I SIGNS & SYMPTOMS

Rheumatologic
ESR, C-reactive protein, antinuclear antibodies, extractable
nuclear antigens, rheumatoid factor, complement, X-rays
Conditions
Polyarteritis (polyarteritis nodosa and microscopic polyangiitis)90% of cases of microscopic polyangiitis are antineutrophil cytoplasmic antibody (ANCA)-positive.
Evaluate polyarteritis nodosa for associated hepatitis B.
Angiography and/or biopsy are confirmatory tests.
Churg-Strauss syndromeThis is defined by presence of
allergic rhinitis, nasal polyposis, asthma, eosinophilia,
and systemic vasculitis of at least 2 extrapulmonary organs.
Palpable purpura is present.
Thromboangiitis obliterans (Buerger disease)Young
adult smokers who have claudication in the lower extremities with ischemic digital injury
Biopsy shows intraluminal thrombus with microabscesses.
Wegener granulomatosisNecrotizing granulomatous
inflammation of the upper and lower respiratory tract,
focal segmental necrotizing glomerulonephritis, skin
lesions (palpable purpura is present)
Can involve the nervous system (sensory neuropathy,
mononeuritis multiplex)
Confirmatory diagnosis is biopsy.
More than 90% of patients are positive for c-ANCA.
Henoch-Schnlein purpuraSmall-vessel vasculitis classically in the setting of abdominal pain with gastrointestinal tract hemorrhage, lower extremity palpable purpura, arthritis, and hematuria
Biopsy shows IgA deposition in vessel walls.
Complement levels are normal.
Leukocytoclastic vasculitisSmall-vessel vasculitis with
immune complex deposition in vessel walls in combination with fibrin and PMNs
Often related to rheumatoid arthritis, Sjgren disease,
systemic lupus erythematosus, and other connective
tissue diseases
Palpable purpura is the classic clinical finding.
207
CryoglobulinemiaType II is frequently associated with

chronic infection (usually hepatitis C) and immune disorders.
Small-vessel vasculitis with palpable purpura, urticaria,
cutaneous ulcers, neuropathy, and arthralgias or arthritis
are common.
Hypersensitivity vasculitisAssociated with drugs, malignancy, or infection
Complement levels (especially C4) may be low.
Neurologic
If a neurologic process is suspected, perform nerve conduction studies, EMG, MRI of spine when indicated.
Musculoskeletal/Traumatic
To evaluate for a musculoskeletal/trauma-related cause,
perform EMG, imaging study (X-ray, CT, MRI), serum
CK.
Neoplastic
Imaging studies (X-rays, CT, MRI)
Biopsy is definitive.
INITIAL MANAGEMENT
Vascular
Acute arterial insufficiency
Thrombolytic therapy if risk factors for bleeding are low
or
Vascular surgery with options including
Percutaneous transluminal angioplasty
Thromboendarterectomy with or without graft replacement
Bypass graft
Phlegmasia alba dolens and phlegmasia cerulea dolens
(venous gangrene)
Massive ileofemoral DVT causing secondary arterial
insufficiency
Phlegmasia alba dolens: swelling, pain, pallor
Phlegmasia cerulea dolens: limbs are cyanotic.
Requires immediate anticoagulation
Consider thrombolytics.
Obtain immediate surgical evaluation for possible
intervention.
208
I SIGNS & SYMPTOMS

If unrecognized and untreated, then excessive morbidity
(including limb amputation)
DVT
Initial treatment is anticoagulation with IV heparin or SQ
low-molecular-weight heparin (LMWH).
Unfractionated heparin can be given as an initial IV
bolus of 60-80 U/kg, followed by continuous infusion
of 14-16 U/kg per hour.
Monitor the PTT in 6 hours, and adjust the infusion
rate accordingly for a goal level that is 1.5-3.0 times
higher than baseline value.
Monitor the PTT every 6 hours after each adjustment
and then every 24 hours once therapeutic levels are
achieved.
Check platelets daily for potential heparin-induced
thrombocytopenia (HIT), with usual onset in 3-4 days.
For patients with HIT, alternatives to heparin include
hirudin or argatroban.
SQ LMWH is an alternative to IV heparin, especially
because it can be used on an outpatient basis.
With LMWH, it is not necessary to measure PTT, but
platelets should be checked during treatment because
HIT can develop.
Dosing of LMWH varies with each derivative used
(e.g., enoxaparin, dalteparin).
Oral anticoagulation with warfarin should begin with 5
mg on the first or second day following heparinization.
Heparin/LMWH therapy should overlap warfarin therapy for 3-5 days after the INR is therapeutic.
Warfarin should be administered for 3-6 months in first
episodes of DVT and lifelong therapy (and thrombophilia
work-up) should be considered if episodes recur.
If DVT is untreated, there is risk of pulmonary embolism.
Infection
Cellulitis, necrotizing fasciitis, gas gangrene, septic arthritis
Initially, treat with broad-spectrum antibiotics and change
on the basis of culture results and sensitivities.
209
Surgical consultation and intervention required for

Necrotizing fasciitis
Gas gangrene (seen with X-rays or appreciated with subcutaneous crepitus)
Septic arthritis
Rheumatologic and Vasculitic

The cornerstone of therapy in most cases of vasculitis is
corticosteroids.
Cytotoxic and antimetabolite drugs are often used in combination with corticosteroids, especially in rapidly progressive or nonsteroid-responsive conditions.
For Buerger disease, treatment is to stop smoking.
For small-vessel vasculitis, treatment of the underlying disease or infection or discontinuation of the offending agent or
drug leads to improvement.
Compartment Syndrome
Increase in closed compartment pressure, with compromise
of local vasculature leading to muscular and neural ischemia.
History and physical exam findings (e.g., pain, pallor, pulselessness, paralysis) are hallmarks for diagnosis.
Measurement of compartment pressures is adjunctive.
Orthopedic surgery evaluation is imperative.
Treatment begins with placing the patient supine to avoid
dependent edema and elevational ischemia.
Fasciotomy is the mainstay of limb salvage.
210
I SIGNS & SYMPTOMS

NAUSEA AND VOMITING
Luke T. Evans, M.D.

Determine if the patient has
A surgical abdomen
A medical emergency manifesting as nausea and vomiting
A central nervous system (CNS) emergency
A life-threatening electrolyte abnormality caused by prolonged nausea and vomiting
Surgical emergencies include
Acute appendicitis
Ascending cholangitis
Bowel infarction
Perforated gastric or duodenal ulcer
Perforated bowel
These emergency conditions are suggested by abdominal
pain, fever, tachycardia, poor urine output, and peritoneal
signs (absent bowel sounds, abdominal rigidity, rebound tenderness, involuntary guarding).
Medical emergencies that may manifest with nausea or vomiting include
Diabetic ketoacidosis
Occult drug overdose
Renal failure
Upper gastrointestinal tract bleeding
Sepsis
Alcohol or drug withdrawal
Pregnancy should also be ruled out early to prevent teratogenic exposures.
Special abbreviation used in this chapter: CNS, central nervous system.

211
CNS emergencies include

CNS hemorrhage or tumor causing increased intracranial
pressure
Encephalitis
Meningitis
CNS emergency conditions are suggested by headache, mental status changes, meningeal signs, and focal neurologic
abnormalities.
Potentially fatal complications of nausea and vomiting include
Severe dehydration
Metabolic alkalosis
Hypokalemia
Hypernatremia
Aspiration
Esophageal rupture
ADDRESSING THE RISK

First, assess airway, breathing, and circulation
AirwayDetermine if patient can protect the airway from
aspiration. If patient is unable to protect the airway, intubate the patient.
BreathingThe patient should be ventilated mechanically if unable to breathe on own.
CirculationTachycardia, hypotension, poor urine output, and fever indicate severe dehydration and/or sepsis.
Begin IV fluid rehydration with normal saline and blood
pressure support with pressors if indicated.
Next, assess for emergencies noted above.
AbdomenExamine for signs of peritonitis. If present,
consult general surgery immediately.
Other complaintsAddress the presence of anginal symptoms, shortness of breath, headache, and neurologic symptoms. Evaluate and treat accordingly.
The differential diagnosis for nausea and vomiting is listed
in Table 1.

Generally, a focused history and physical exam are needed
to evaluate new or persistent nausea and/or vomiting.
212
I SIGNS & SYMPTOMS
Historical clues to the cause of nausea and/or vomiting are

listed in Table 2.
Physical exam findings to narrow the differential diagnosis
Vital signs, including orthostatics, to assess for systemic
inflammatory response syndrome and dehydration
Mental statusassess ability to protect airway from
aspiration.
Agitation, somnolence, hallucinations, and confusion
suggest toxin ingestion.
Intake and output to assess fluid status
Jaundice and/or scleral icterus suggest cirrhosis, hepatitis,
or biliary obstruction.
Fruity smell of ketones suggests ketoacidosis.
Neurologic exam to identify focal cranial nerve or cerebellar abnormalities, meningismus suggesting meningitis,
or intracranial mass or intracranial bleed
Ophthalmoscopic exam to look for papilledema suggesting increased intracranial pressure
Abdominal examLook for the presence and character of
the following:
Bowel sounds
Rebound tenderness
Guarding
Peritoneal signs
Murphy sign
Tenderness over McBurney point
Obturator sign
Hernias
Flank pain
Rectal exam, including occult blood testing, to rule out
fecal impaction and occult blood loss

The work-up for serious or persistent nausea and vomiting
should include
Flat and upright or left lateral decubitus X-rays
CBC with differential count
Electrolytes (sodium, potassium, chloride, bicarbonate,
213
Table 1. Differential Diagnosis for Nausea and Vomiting

Surgical emergencies associated with nausea & vomiting
Bowel obstruction
Perforated viscus
Acute appendicitis
Acute cholecystitis
Intracranial hemorrhage
Incarcerated hernia
Mesenteric ischemia
Central nervous system
hemorrhage
Increased intracranial pressure (tumor, pseudotumor)
Medical emergencies associated with nausea & vomiting

Upper gastrointestinal tract
bleeding
Digoxin toxicity
Renal failure
Acute pancreatitis
Acute cholangitis
Toxin ingestion
Alcohol withdrawal
Sepsis
Meningitis
Peritonitis
Hypercalcemia
Nonemergency causes of nausea & vomiting

Infectious causes
Motility disorders (continued)
Viral
Constipation
Rotavirus
Autonomic insufficiency
Norwalk agent
Chronic intestinal pseudoBacterial enterotoxinobstruction
mediated
Gastroesophageal reflux
Staphylococcus aureus
disease
Bacillus cereus
Systemic conditions
Clostridium perfringens
Pregnancy
Iatrogenic causes
Hyperemesis gravidarum
Narcotics
Hypertensive urgency
Digoxin
Idiopathic cyclic vomiting
Theophylline
Porphyria
Chemotherapy
Primary central nervous system
Antibiotics
cause
NSAIDs
Benign positional vertigo
Radiation enteritis
Motion sickness
Metabolic derangements
Labyrinthitis (Meniere
Hyperthyroidism
disease)
Addison disease
Migraine headache
Motility disorders
Psychiatric conditions
Gastroparesis (diabetic &
Anxiety
others)
Bulimia
Ileus
Anorexia nervosa
Collagen vascular disorders
Rumination syndrome
Postgastric surgery
214
I SIGNS & SYMPTOMS
BUN, creatinine, glucose, calcium, magnesium, phosphorus)

Liver chemistry panel (alkaline phosphatase and ALT)
Amylase and lipase
If the patient is female, determine -human chorionic
gonadotropin to rule out pregnancy.
If abdominal pain is present, consider CT or ultrasound of
the abdomen, urinalysis with culture, INR, and serum lactate level.
If a headache, local neurologic signs, or altered mental
status is present, consider CT of the head, lumbar puncture,
toxicology screen, and gastric lavage.
If fever is present, consider blood cultures, urinalysis with
culture, abdominal CT or ultrasound, and chest X-ray.
If the patient is diabetic, obtain a stat finger-stick glucose
value, serum ketones, and arterial blood gases to rule out
diabetic ketoacidosis.
If bleeding is from the gastrointestinal tract, type and
crossmatch for blood transfusion and obtain INR and
PTT.
For chronic nausea and vomiting, consider
Esophagogastroduodenoscopy to rule out peptic ulcer
disease
Gastric emptying study to rule out gastroparesis
Small-bowel follow-through study to rule out a partial
small-bowel obstruction
INITIAL MANAGEMENT
Management must address the primary cause of nausea and
vomiting while treating ongoing symptoms and complications.
Gastroenteritis
IV fluid resuscitation
Monitoring of electrolytes
Antiemetic therapy with phenothiazines (prochlorperazine
[Compazine] or promethazine [Phenergan])
Small-bowel obstruction
Nasogastric tube to low intermittent suction
NPO
Serial abdominal exams
215
216
Table 2. Historical Clues to Cause of Nausea and/or Vomiting

Temporal characteristics
Presence & character of

abdominal pain
Diabetes mellitus
Historical clues
Suggestive of
Nausea & vomiting with fever or diarrhea

Pain precedes nausea, vomiting, &
distension
Reproducible postprandial pain with
history of vasculopathy
Early morning vomiting with morning
headache
Early morning nausea & vomiting
Gastroenteritis
Mechanical obstruction
Stool studies
Flat & upright abdominal X-ray
Mesenteric ischemia
Doppler ultrasound of abdomen

or mesenteric angiography
Head CT
Colicky pain (intermittent)

Pain out of proportion to abdominal exam
Well-localized pain with jostling
movement
Polyuria, polydipsia, & weight loss
Obstructed viscus
Mesenteric ischemia
Peritoneal irritation
-HCG
Confirm viability of pregnancy
Flat & upright abdominal X-ray
CT or mesenteric angiography
Abdominal CT
Untreated/undiagnosed
diabetes DKA
Diabetic gastroparesis or
mesenteric vasculopathy
Serum glucose, serum pH,

serum ketones
Gastric emptying study/
mesenteric angiogram
Long-term poor glucose control
Increased intracranial
pressure
Pregnancy
Supportive tests
Table 2 (continued)
Infectious
Suggestive of
Supportive tests
S. aureus gastroenteritis
Contaminated food can be

cultured
B. cereus gastroenteritis
Stool culture for organism
Acute coronary syndrome

Intentional overdose
ECG & cardiac enzymes

Gastric lavage, drug screen,
including acetaminophen
level
Alcohol dependence or history of

withdrawal
New or increased doses of medications
(especially narcotics, chemotherapy,
& antibiotics)
Alcohol withdrawal
DKA, diabetic ketoacidosis; HCG, human chorionic gonadotropin.
Medication side-effect
217
I SIGNS & SYMPTOMS
Cardiopulmonary
Miscellaneous
Historical clues
Nausea, vomiting, & diarrhea 1-6 hours
after a meal (ham, potato or egg
salad, cream pastries, & poultry)
Nausea, vomiting, & diarrhea 1-6 hours
after eating fried rice or refried beans
Anginal symptoms, dyspnea
Altered mental status previous suicide
attempts
IV fluid resuscitation with additional fluid to match

nasogastric output
Surgical consultation
Chemotherapy
IV fluid resuscitation
Antiemetic therapy with 5-HT3 receptor antagonists
Dexamethasone and lorazepam may also be helpful.
Motion sickness or vestibular disturbances
Antiemetic therapy with antihistamines
Adverse drug reactions
Consider discontinuing drug.
Antiemetic therapy with phenothiazines
MANAGEMENT OF COMPLICATIONS OF NAUSEA AND

VOMITING
Intravascular depletionResuscitate with normal saline.
HypokalemiaReplace potassium IV or PO, and monitor
for cardiac events.
HyponatremiaResuscitate with normal saline. (See chapter on Electrolyte Disturbances.)
Metabolic alkalosisLimit nasogastric suctioning if possible and replete intravascular space.
Esophageal mucosal tear (Mallory-Weiss tear)Treat the
same way as a gastrointestinal tract bleed.
Esophageal rupture (Boerhaave syndrome) characterized by
severe epigastric pain, cyanosis, dyspnea, subcutaneous or
mediastinal emphysema, a left-sided pleural effusion, and
dyspneaObtain an emergency general or thoracic surgery
consult for consideration of thoracotomy and esophageal
repair.
Aspiration
Intubate if the patient is unable to protect own airway.
Provide aggressive pulmonary hygiene.
Consider initiating antimicrobial coverage if you are certain of aspiration and the patient is experiencing respiratory distress.
218
I SIGNS & SYMPTOMS

OCULAR AND VISUAL ABNORMALITIES
Sanjay V. Patel, B.M., B.S.
Jonathan M. Holmes, B.M., B.Ch.
IS THE PATIENTS VISION AT RISK?

Immediate intervention for the following conditions can save
vision:
Acute angle-closure glaucoma
Giant cell arteritis causing either
Anterior ischemic optic neuropathy or
Central retinal artery occlusion
Nonarteritic central retinal artery occlusion
Endophthalmitis
Corneal ulcer and/or infectious keratitis
Retinal detachment
ADDRESSING THE RISK
For any ocular or visual complaint
Measure visual acuity in each eye. Use distance or near
chart, and test each eye separately, with patient wearing his
or her usual glasses if available.
Has visual acuity changed from previously? By patient
history? By previous and current examination?
Check the eye history for previous documented visual
acuity.
Is the complaint acute or chronic, unilateral or bilateral?
Does the patient have a systemic disorder that could be
related to the visual problem, e.g., hypertension, diabetes
mellitus, hypercoagulable state, rheumatoid arthritis, other
autoimmune disease?
Does the patient have a history of recent eye trauma, injury,
foreign body, or eye surgery?
Special abbreviation used in this chapter: RAPD, relative afferent pupillary

defect.
219
Does the patient wear contact lenses? If so, is the patient

wearing them now?
For the red eye
Is the eye painful or painless?
Painless sectoral redness suggests subconjunctival
hemorrhage.
Most other causes of red eye are inflammatory and,
thus, cause discomfort.
Grittiness, itching, or a foreign body sensation suggests a surface problem (tear film defect, conjunctivitis, or true foreign body).
Deep, severe, boring pain or photophobia suggests a
deeper problem (scleritis, keratitis [corneal inflammation], uveitis, endophthalmitis, or acute glaucoma).
How is the redness distributed?
Redness can be localized or diffuse.
Diffuse conjunctival redness, involving the entire conjunctiva, suggests conjunctivitis.
Redness at the corneoscleral junction (or limbus) is
termed ciliary flush, and when more pronounced than
the surrounding injection, it suggests a more serious
corneal or intraocular process (e.g., keratitis or uveitis).
These conditions are often associated with severe pain.
Has vision changed?
More serious conditions are often, but not always, associated with decreased visual acuity. Halos suggest
corneal edema, e.g., in acute glaucoma.
Is there a hypopyon (layer of white cells within the anterior chamber)?
It is associated with very severe disease.
It suggests corneal inflammation (e.g., infectious keratitis) or intraocular inflammation (e.g., uveitis or
endophthalmitis).
Is the cornea cloudy (caused by corneal edema and may
be recognized as obscured iris details)?
It suggests acute glaucoma or keratitis.
A distinct white spot (infiltrate) on the cornea may represent an acute corneal ulcer.
If the defect is dendritic in shape, suspect herpes simplex keratitis.
If the defect is associated with a white infiltrate, a
220
I SIGNS & SYMPTOMS
corneal ulcer or microbial keratitis is likely.

Any epithelial defect not associated with trauma is
cause for concern.
How do the pupils look?
Anterior uveitis can cause miosis (constriction) or an
irregular margin (due to posterior synechiae, i.e., adherence of the pupillary margin to the lens).
Acute glaucoma often causes a semidilated and fixed
pupil.
Check previous documentation of the pupils in the eye
history.
Careful documentation of the pupil exam is important.
Remember that pupils can remain dilated, fixed, or
irregular after previous ocular surgery.
For the eye with painless visual loss (quiet white eye)
This suggests a posterior segment process, i.e., retina or
optic nerve.
Assess visual fields to confrontation.
A vertical field cut most likely represents a chiasmal
or postchiasmal lesion.
A horizontal field cut (altitudinal defect) most likely
represents optic neuropathy (e.g., optic neuritis).
A central scotoma suggests optic or retrobulbar neuritis or macular disease.
A retinal detachment can cause any pattern of field
defect in the affected eye.
Are the red reflexes present and symmetric?
Absence of a red reflex is due to media opacity (e.g.,
corneal opacity, cataract, vitreous hemorrhage, or retinal
detachment).
Is there a relative afferent pupillary defect (RAPD)?
This is detected with the swinging flashlight test.
RAPD suggests an asymmetric large retinal lesion (e.g.,
large retinal detachment) or an asymmetric optic nerve
lesion (e.g., ischemic optic neuropathy).
Examine and compare both fundi, looking for symmetry and
asymmetry between optic discs, veins, arterioles, maculae,
and peripheral retinae.
221
Look for pallor of the macula (edema) surrounding the

classic cherry-red spot of a central retinal artery occlusion.
Look for the swollen optic disc of acute anterior ischemic
optic neuropathy or increased intracranial pressure.
Look for the cloudy vitreous and poor view of the retina
in an inflamed eye with endophthalmitis or in a diabetic
person with a vitreous hemorrhage.
The differential diagnoses for painful red eye and loss of
vision in a quiet white eye are listed in Table 1.

For painful red eye and for loss of vision in a quiet white
eye, see Tables 2 and 3, respectively.
ORDERING TESTS
Diagnosis of visual abnormalities is made primarily by history
and exam, including inspection, red reflex, ophthalmoscopy.
Table 1. Differential Diagnoses for Painful Red Eye and for

Sudden Loss of Vision in a Quiet White Eye
Painful red eye
Conjunctivitis (with or without
blepharitis)
Exposure keratopathy
Abrasion or foreign body
associated with trauma
Keratitis (infectious or
noninfectious)
Episcleritis
Scleritis
Acute anterior uveitis or iritis
Acute angle-closure glaucoma
Posterior uveitis
Endophthalmitis
Hyphema (usually
posttraumatic)
Subconjunctival hemorrhage
(not painful)
222
Sudden loss of vision in a

quiet white eye
Vitreous hemorrhage, e.g.,
diabetes mellitus
Central or branch retinal artery
occlusion
Central or branch retinal vein
occlusion
Anterior ischemic optic neuropathy (arteritic or nonarteritic)
Optic or retrobulbar neuritis
(pain with eye movement)
Exudative age-related macular
degeneration
Retinal detachment
I SIGNS & SYMPTOMS
When possible, measure intraocular pressure (unless you

suspect severe trauma to the eye, when it should be assessed
by the ophthalmologist).
Ophthalmologist should perform specialized tests, including slit-lamp exam.
Diagnosis and management of suspected arteritic ischemic
optic neuropathy or arteritic central retinal artery occlusion
are aided by ESR (>50 mm/hour by Westergren method)
and increased C-reactive protein, and diagnosis is confirmed
by temporal artery biopsy.
MANAGEMENT
Management of painful red eye is described in Table 4.
Management of loss of vision in a quiet white eye is described
in Table 5.
Table 2. Painful Red Eye

Features
Blurriness, cleared with blinking
Purulent or watery discharge
Eyelids stick together
Slight discomfort of foreign body sensation
Upper respiratory tract infection
May be associated with blepharitis
May be itchy if allergic cause
Usually viral, may be bacterial
Usually bilateral
Diffuse conjunctival (not ciliary) injection
Discharge
Diagnosis
Conjunctivitis
223
Table 2 (continued)
Features
Diagnosis
Localized redness, almost always painless

Localized redness concealing conjunctival
vessels (may be diffuse or patchy)
Visual acuity unchanged
Idiopathic or associated with coughing,
straining, bleeding dyscrasias,
anticoagulant or antiplatelet agents,
hypertension, trauma
Subconjunctival
hemorrhage
Painless or dull ache

Young adult
Localized sectorial redness
Dilated vessels that blanch with
phenylephrine 2.5% drops
Visual acuity unchanged
Idiopathic or associated with collagen
vascular disease, gout, herpes zoster
May be recurrent
Episcleritis
Blurred vision
Severe deep pain
Headaches
Photophobia
Dilated scleral vessels that do not blanch
with phenylephrine, sectorial or diffuse
Scleral nodules
Decreased visual acuity
Violacious hue
Associated with connective tissue disease
or granulomatous systemic disease
(particularly rheumatoid arthritis,
Wegener granulomatosis)
May be recurrent
224
Scleritis
I SIGNS & SYMPTOMS

Table 2 (continued)
Features
Pain or deep ache
Blurred vision
Photophobia
Usually unilateral
Visual acuityunchanged or decreased
Ciliary flush
Miosis or irregular pupil (posterior
synechiae)
Small deposits on cornea (keratic
precipitates)
Cloudy anterior chamber & hypopyon
if severe
Idiopathic or associated with systemic
disease, e.g., HLA-B27related
disorder, inflammatory bowel disease,
juvenile rheumatoid arthritis, Behet
syndrome, sarcoidosis
If history of intraocular surgery, trauma,
or sepsis, consider endophthalmitis
May be recurrent
Pain
Photophobia
Poor vision
Unilateral
Ciliary flush
Corneal infiltrate (white opacity in
corneal stroma)
Corneal epithelial defect (stains with
fluorescein)
May have hypopyon
May have purulent discharge
If dendritic stain pattern, herpes simplex
virus is likely
Associated with corneal injury, contact
lens wear, immunosuppression
In noninfectious keratitis, infiltrate parallel
to limbus, with or without ulceration,
associated with Wegener granulomatosis,
rheumatoid arthritis, severe blepharitis
Diagnosis
Anterior uveitis
(iritis)
Keratitis
225
Table 2 (continued)
Features
Irritation
Foreign body sensation
Dryness
Poor blinking
Redness
Corneal infiltrate if superimposed
infection
Associated with CN VII palsy, sedation
(ICU), proptosis
Particularly severe if associated with
CN V palsy
Intense pain or ache
Poor vision, halos
Headache
Nausea & vomiting
Unilateral
Corneal edema (cloudy)
Shallow anterior chamber
Semidilated & fixed pupil
Globe feels stony-hard to palpation
Associated with hyperopia (farsightedness), elderly age, pupillary dilation
Floaters
Blurred vision
Photophobia
Occasionally redness or pain
Unilateral
Vitreous cells or opacities
Retinal exudates
Scarring
Pigmentation
Associated with toxoplasmosis,
sarcoidosis, cytomegalovirus, others
226
Diagnosis
Exposure
keratopathy
Acute angleclosure
glaucoma
Posterior uveitis
I SIGNS & SYMPTOMS

Table 3. Loss of Vision in a Quiet White Eye
Features
Unilateral acute loss of vision
Painless
Sometimes history of amaurosis fugax
Relative afferent pupillary defect
Pale retina (sectorial if only a branch
is occluded)
Cherry-red spot at macula
Narrow retinal arterioles arteriolar emboli
May have other symptoms of giant cell
(i.e., temporal) arteritis (jaw claudication,
headache, polymyalgia)
Unilateral acute loss of vision
Painless
Tortuous dilated retinal veins
Diffuse flame-shaped retinal hemorrhages
Cotton wool spots
Disc edema
Neovascularization (late)
Associated with hypertension, atherosclerosis of adjacent artery, glaucoma,
hypercoagulable state, vasculitis
Sudden decrease in vision, with
appearance of floaters or webs
Loss of red reflex
Poor retinal view because of blood
in vitreous
If mild, partial retinal obscurity &
evidence of underlying retinopathy
Associated with proliferative diabetic
retinopathy, sickle cell disease,
subarachnoid hemorrhage, retinal or
vitreous detachment, vein occlusion,
trauma
Diagnosis
Occlusion of
central or
branch retinal
artery (must
exclude giant
cell arteritis)
Occlusion of
central or
branch retinal
vein
Vitreous
hemorrhage
227
Table 3 (continued)
Features
Flashes & floaters
Curtain across vision impairing central
& peripheral vision
Visual field defect
May have relative afferent pupillary defect
Elevation of retina
Retinal tear
Myopia
Sudden unilateral visual loss
Temporal headache
Jaw claudication
Systemic symptoms associated with
polymyalgia rheumatica
Scalp tenderness
Nonpulsatile temporal arteries
Optic disc swelling pallor
Altitudinal field defect
Markedly increased ESR & C-reactive
protein
Sudden unilateral visual loss
Altitudinal visual field loss (classically
inferior)
Optic disc swelling (may be partial
in accordance with field defect pallor)
Normal ESR
Idiopathic or may be associated with
arteriosclerosis, diabetes, hypertension
228
Diagnosis
Retinal
detachment
Arteritic anterior
ischemic optic
neuropathy
Nonarteritic
anterior
ischemic optic
neuropathy
I SIGNS & SYMPTOMS

Table 3 (continued)
Features
Diagnosis
Subacute visual loss (days)

Usually unilateral
Impaired color vision
Pain with eye movement
Young adult
Color (red) desaturation
Optic disc swelling pallor
Variable field defect
Fundus may be normal
Idiopathic or may be associated with
multiple sclerosis, post-viral
infections, granulomatous disease
Optic neuritis
If no fundus
abnormality,
then retrobulbar neuritis
Sudden loss of central vision

Central scotoma
Distortion of straight lines
Objects appear distorted
Macular retinal & subretinal
hemorrhages (gray-green subretinal
membrane)
Drusen & pigmentation at macula
Exudative agerelated macular

degeneration
Gradual loss of central vision (chronic)

Usually bilateral
Drusen & pigmentation at macula
Dry age-related
macular degeneration
229
Table 4. Management of Painful Red Eye

Diagnosis
Conjunctivitis
Subconjunctival hemorrhage
Episcleritis
Scleritis
Anterior uveitis
(iritis)
Endophthalmitis
Keratitis
Exposure
keratopathy
Acute angleclosure
glaucoma
Posterior uveitis
230
Management
Trimethoprim-polymyxin B drops or
erythromycin ointment
But most cases of conjunctivitis are viral or
allergic & can be treated symptomatically
with artificial tears
If contact lens wearer, lenses should be
removed for at least 7 days
If purulent, consider culture to rule out
gonococcus
If resistant to antibiotic treatment, consider
Chlamydia infection
No treatment, check for underlying cause
if recurrent
Mildmay resolve spontaneously
Moderatetry topical NSAID, e.g., ketorolac
tromethamine
Severerefer to ophthalmologist for topical
steroid treatment
Urgent referral to ophthalmologist for systemic
steroid treatment and/or oral NSAID
Refer to rheumatology for systemic work-up
In severe cases, immunosuppression may be
needed
Urgent referral to ophthalmology for topical
steroids
Cycloplegic/mydriatic agents help with
discomfort & prevent posterior synechiae
Consider associated systemic disorders
Refer immediately to ophthalmology for
vitreous aqueous culture and intravitreal
antibiotics
Immediate referral to ophthalmologist
Will require culture of corneal scrapings &
aggressive topical antibiotic, antifungal,
antiviral treatment
Keep the cornea moist: frequent artificial
teardrops or lubricant ointment
Refer to ophthalmology if no response to lubrication or secondary infection is suspected
Immediate referral to ophthalmology
Treat with timolol 0.5% drops, acetazolamide
500 mg IV, consider mannitol 1-2 g/kg IV
over 60 minutes
Topical steroids & pilocarpine per ophthalmology
May need laser iridotomy or surgery
Urgent referral to ophthalmology
Consider associated systemic disorders
I SIGNS & SYMPTOMS

Table 5. Treatment of Loss of Vision in a Quiet White Eye
Central or
branch
retinal
artery
occlusion
Best treatment results are with earliest intervention

Immediate referral to ophthalmology
Immediate digital massage of globe, acetazolamide 500 mg IV, timolol 0.5% drops to reduce
pressure
Ophthalmologist to consider anterior chamber
paracentesis
Immediate ESR, C-reactive protein, & systemic
steroids if giant cell arteritis suspected
Central or
Early referral to ophthalmology to determine if
branch
ischemic vein occlusion for treatment to
retinal vein
reduce risk of neovascular glaucoma
occlusion
Treat underlying conditions (e.g., diabetes &
hypertension)
Vitreous
Bed rest, elevate head of bed
hemorrhage
Stop antiplatelet agents or anticoagulants if
possible
Immediate ophthalmology referral for ultrasound
investigation of posterior pole to exclude retinal
detachment
If diabetic, likely to be due to proliferative
retinopathy but retinal detachment must be ruled
out immediately
Retinal
Strict bed rest with bilateral eye patching if
detachment
macula is threatened
Immediate referral to ophthalmology for surgery
Arteritic anteri- High-dose oral prednisone (60-100 mg daily)
or ischemic
Start steroids before ESR & C-reactive protein
optic neurop- results are known
athy (AION) Refer to ophthalmology; should have temporal
artery biopsy within 1 week
Nonarteritic
Rule out arteritic AION; if unsure, ESR, CAION
reactive protein, & biopsy, treat as arteritic with
steroids until diagnosis made
Nonarteritic AION cannot be treated; management
of underlying disorder is required
Optic neuritis/ Check for focal neurologic signs & refer to
retrobulbar
neurologist if present
neuritis
Order MRI (predictive value for multiple
sclerosis)
Ophthalmology referral is also indicated
IV steroids may increase rate of recovery
(methylprednisolone 1 g/day IV for 3 days,
then prednisone 1 mg/kg/day PO 11 days)
231
Table 5 (continued)
Exudative age- Urgent referral to ophthalmology for potential
related
laser, surgical, or drug treatment
macular
degeneration
Dry ageIs not an emergency
related
Routine ophthalmology referral
macular
degeneration
232
I SIGNS & SYMPTOMS

PALPITATIONS
Kevin A. Bybee, M.D.
Stephen L. Kopecky, M.D.

Palpitations
This refers to conscious sensation of cardiac activity.
Can signify a primary cardiac problem or can be of noncardiac origin
Can be symptom of a benign process, life-threatening
arrhythmia, or serious underlying noncardiac disorder
Patient with palpitations must be evaluated quickly to rule out
arrhythmia or other serious disorder.
Because any patient with a tachyarrhythmia and hemodynamic instability needs urgent cardioversion, initial evaluation should focus on indications for emergent electrical
cardioversion.
ADDRESSING THE RISK
Obtain a stat 12-lead ECG.
On history, assess if the patient has symptoms of a hemodynamically significant arrhythmia such as chest pain, dyspnea, presyncope, or confusion.
Assess for hemodynamic stability: tachycardia, hypotension, hypoxia, or changes in mental status.
Focus the physical exam on vital signs and the cardiorespiratory systems.
Determine heart rate and rhythm.
Is the patient tachycardic?
If so, is the rhythm regular or irregular; if irregular, is it
regularly irregular or irregularly irregular?
Look for signs of heart failure and depressed cardiac output, e.g., hypoxemia, increased jugular venous pressure,
Special abbreviation used in this chapter: AV, atrioventricular.

233
presence of third heart sound (S3) gallop, bibasilar crackles, cyanosis, impaired peripheral perfusion.
Call for code team response if the patient has signs or symptoms of a hemodynamically significant arrhythmia.
Place supplemental oxygen at 3-4 L by nasal cannula.
Establish IV access.
Efficiently and accurately interpret the 12-lead ECG.
Tachyarrhythmias >150 beats/minute and bradyarrhythmias
<50 beats/minute when associated with hypotension signify
a hemodynamically significant arrhythmia.
Evaluate for and address life-threatening noncardiac causes
of palpitations: sepsis, hypoglycemia, severe anemia, acute
blood loss (gastrointestinal tract bleed, retroperitoneal bleed),
thyrotoxicosis, adrenal insufficiency, pheochromocytoma.
The differential diagnosis for palpitations of arrhythmic
origin is listed in Table 1 and that for palpitations of nonarrhythmic origin, in Table 2.

ECG Interpretation
Regular Tachycardia With Narrow QRS Complex (<0.10 ms)
Sinus tachycardia
Atrioventricular (AV) nodal reentrant tachycardia
AV reentrant tachycardia with orthodromic conduction
(Wolff-Parkinson-White syndrome)
Atrial flutter with fixed conduction
Regular Tachycardia With Wide QRS Complex (>0.12 ms)
Sinus tachycardia with delayed or aberrant conduction (sinus
tachycardia with a bundle branch block)
Atrial flutter with fixed conduction and delayed or aberrant
conduction
Supraventricular tachycardia with delayed or aberrant
conduction
Ventricular tachycardia
AV reentrant tachycardia with antidromic conduction
Irregular Tachycardia With Narrow QRS Complex

Atrial fibrillation
234
I SIGNS & SYMPTOMS
Atrial flutter with variable conduction

Multifocal atrial tachycardia
Sinus rhythm with frequent atrial premature contractions
Sinus rhythm with frequent premature ventricular contractions, which will have a wide QRS
Irregular Tachycardia With Wide QRS Complex

Atrial fibrillation with delayed or aberrant conduction
Atrial flutter with variable conduction and delayed or aberrant conduction
Torsades de pointes
Note: If the patient has known coronary artery disease and a
wide complex tachycardia, assuming it is ventricular tachycardia will be correct >90% of the time.
Sinus Tachycardia
Can be a secondary response to many underlying conditions
Sepsis
Fever
Hypovolemia
Hypoxia
Thyrotoxicosis
Anemia
Table 1. Differential Diagnosis for Palpitations of

Arrhythmic Origin
Tachyarrhythmia
Sinus tachycardia
Atrial fibrillation
Atrial flutter
Paroxysmal supraventricular
tachycardia
Atrioventricular reentrant
tachycardia (Wolff-ParkinsonWhite syndrome)
Bradyarrhythmia
Sinus bradycardia
Second-degree heart block
(Mobitz II)
Third-degree heart block
Vagal (cardioinhibitory)
bradycardia
235
Table 2.
Differential Diagnosis for Palpitations of

Nonarrhythmic Origin
Noncardiac
Sepsis
Fever
Anemia
Thyrotoxicosis
Hypoglycemia
Anxiety/postoperative pain
Pheochromocytoma
Medications (theophylline,
albuterol, other stimulants)
Diaphragmatic flutter
Cardiac
Atrial septal defect
Ventricular septal defect
Aortic regurgitation
Aortic stenosis
Pericarditis
Hyperkinetic heart syndrome
Acute mitral regurgitation
Hypoglycemia
Adrenal insufficiency (addisonian crisis)
Stimulants (albuterol, theophylline, cocaine, amphetamines)
Anxiety or pain
ORDERING TESTS
All patients complaining of palpitations need immediate
evaluation, including a stat bedside 12-lead ECG.
Tests for various suspected diagnoses are listed in Table 3.
INITIAL MANAGEMENT
Arrhythmia Management
Place patient on continuous bedside monitor with 3 limb
leads.
Obtain IV access if not already available, and place supplemental oxygen.
Refer to American Heart Association ACLS algorithms for
detailed arrhythmia management information.
The following are suggestions for initial arrhythmia management with first-line treatments.
TachyarrhythmiaUnstable
Considered unstable if chest pain, dyspnea, mental status
change, hypotension, shock, pulmonary vascular congestion, or acute myocardial infarction
Consider electrical cardioversion.
236
I SIGNS & SYMPTOMS

Table 3. Suspected Diagnosis and Tests Ordered
Suspected diagnosis
Tests/lab
Myocardial infarction,
arrhythmia
12-lead ECG, CK, CK-MB, troponin

I or T, CBC, electrolytes (magnesium,
creatinine, sTSH)
sTSH, free T4, total T3
CBC, stool hemoccult, ferritin, serum
iron, total iron-binding capacity,
peripheral blood smear, reticulocyte
count
Blood cultures 2, chest X-ray,
urinalysis with Gram stain & culture,
CBC
Transthoracic echocardiogram, ECG
Serum cortisol, cosyntropin stimulation
test, electrolytes
Thyrotoxicosis
Anemia
Sepsis
Valvular heart disease

Adrenal insufficiency
T3, triiodothyronine; T4, thyroxine; sTSH, sensitive thyroid-stimulating

hormone.
Indications for cardioversion are hypotension, chest pain,

congestive heart failure, or depressed cerebral perfusion
manifested as change in mental status.
Use unsynchronized cardioversion for all unstable tachyarrhythmias without a pulse.
TachyarrhythmiaStable
Considered stable if no chest pain, dyspnea, mental status
change, hypotension, shock, pulmonary vascular congestion, or acute myocardial infarction
Atrial fibrillation/flutter
Diltiazem (Cardizem)
Bolus IV 0.12-0.25 mg/kg or 10-20 mg IV over 2 minutes
Repeat in 15 minutes if needed.
Consider diltiazem drip at 5-15 mg/hour.
Paroxysmal supraventricular tachycardia
Consider vagal maneuvers if not contraindicated.
Adenosine, 6 mg IV push and quickly flush with normal
saline; repeat with 12 mg IV push if no response.
237
Consider verapamil, 2.5-5.0 mg, if narrow QRS and no

response to adenosine.
Consider lidocaine, 1.0-1.5 mg/kg IV, if wide QRS and
no response to adenosine.
Wide complex tachycardia of uncertain type
Lidocaine, 1.0-1.5 mg/kg IV; repeat 0.5-0.75 mg/kg if
needed.
Start maintenance lidocaine infusion 2-4 mg/minute if
initial response to lidocaine.
Consider adenosine, 6-12 mg IV, if no response to lidocaine.
Consider procainamide, 20-30 mg/minute (maximum 17
mg/kg), if no response to adenosine.
Lidocaine, 1.0-1.5 mg/kg IV push; repeat 0.5-0.75 mg/kg
if needed.
Start lidocaine infusion, 2-4 mg/minute, if initial response
to lidocaine.
Consider procainamide if no response to lidocaine.
Torsades de pointes
Magnesium sulfate 2 g IV
If no response to magnesium, consider atrial or ventricular pacing.
BradyarrhythmiaUnstable
Considered unstable if chest pain, dyspnea, mental status
change, hypotension, shock, pulmonary venous congestion,
or acute myocardial infarction
Atropine, 0.5-1.0 mg IV
Use transcutaneous pacemaker as a bridge (verify patient
tolerance, may need analgesia and sedation).
Prepare for transvenous pacemaker insertion.
BradyarrhythmiaStable
Considered stable if no chest pain, dyspnea, mental status
change, hypotension, pulmonary venous congestion, or acute
myocardial infarction
Consider atropine, 0.5-1.0 mg IV, or observe.
Monitor and follow vital signs closely.
Ensure availability of transcutaneous pacing if needed.
238
I SIGNS & SYMPTOMS

RASH
Rochelle R. Torgerson, M.D., Ph.D.
Lisa A. Drage, M.D.

Although most rashes may be managed in an outpatient setting, there are instances when an acute presentation or flare
of a chronic condition requires intensive therapy.
Rashes That Require Inpatient CareTwo General
Categories
Rashes that cause altered metabolism and have a considerable
risk of infection
Rashes that are key diagnostic clues to major underlying illnesses
Presence of the Following Indicate Increased Severity
Angioedema and tongue swelling
Mucous membrane involvement
Skin pain or tenderness
Generalized erythema
Extensive blistering, bullae, or desquamation
Systemic symptoms: fever, hypotension, headache, myalgias,
arthralgias
Systemic involvement: lymphadenopathy, nephritis, hepatitis,
agranulocytosis
Immunosuppression
ADDRESSING THE RISK

If airway compromise or hypotension
Airway, breathing, circulation (ABCs)
Severe desquamation or blistering
Special abbreviation used in this chapter: ABCs, airway, breathing, circulation.

239
Fluid resuscitation, aseptic technique, topical or systemic

antibiotics
ICU if hemodynamically unstable
If infectious cause
Cultures, broad-spectrum antibiotic coverage
Blistering or urticaria/angioedema (not infectious)
Systemic corticosteroids (after appropriate diagnostic cultures/studies)
The extensive differential diagnosis can be grouped according to the morphology of individual skin lesions.
Terms used to describe skin lesions are listed in Table 1.
Causes of rash are listed in Table 2.
The differential diagnosis is listed in Table 3.

Relevant Information to Obtain From the History
Rash: onset, location, spread, associated symptoms (e.g.,
itch, pain)
Systemic symptoms: fever, headache, myalgia, arthralgia
Medications: recent changes as well as current oral, topical,
over-the-counter, herbal
Previous skin diseases or reactions
Allergies: drug or contact
Exposures: sick contacts, travel, animals, bugs, food
Family history: atopic or psoriasis
Immune status
Table 1. Terms Used to Describe Skin Lesions

Term for lesion
Macule
Papule
Vesicle
Bulla
Pustule
Scale
Purpura
Wheal (hive)
240
Appearance
Flat, color variation from surrounding skin
Elevated, diameter = 0.5 cm
Fluid-filled (clear) blister, diameter 0.05 cm
Fluid-filled (clear) blister, diameter >0.05 cm
Pus-filled blister
Dry, thickened flakes of stratum corneum
Purple, nonblanchable, macular (nonpalpable) or
papular (palpable)
Indurated papule, central pallor, evanescent
I SIGNS & SYMPTOMS

Table 2. Causes of Rash
Generalized
Dermatomyositis
Drug eruption
Lupus erythematosus
Photosensitive
eruptions
Szary syndrome
(cutaneous T-cell
lymphoma)
Stevens-Johnson
syndrome
Toxic epidermal
necrolysis
Viral exanthem
Patterned/localized
erythema
Abscess & furuncle
Cellulitis
Erythema migrans
Erythema multiforme
Erythema nodosum
Urticaria
Purpura
Actinic purpura
Steroid-associated
purpura
Thrombocytopenic
purpura
Trauma-associated
purpura
Vasculitis (palpable
purpura)
Vesicles and bullae
Pustules
Inflammatory papules
Bullous impetigo
Bullous pemphigoid
Contact dermatitis
(acute)
Coxsackievirus
Dermatitis herpetiformis
Herpes simplex
Herpes zoster
Pemphigus vulgaris
Porphyria cutanea
tarda
Varicella
Infectious
Bacterial
Fungal
Noninfectious
Pustular psoriasis
Drugs
Insect bite reactions

Lichen planus
Miliaria
Scabies
Eczematous rashes
Atopic dermatitis
Contact dermatitis
Lichen simplex
chronicus
Seborrheic dermatitis
Stasis dermatitis
Scales
White spots
Discoid lupus
erythematosus
Fungal infections
Mycosis fungoides
(cutaneous T-cell
lymphoma)
Pityriasis rosea
Psoriasis
Secondary syphilis
Pityriasis alba
Postinflammatory
hypopigmentation
Tinea versicolor
Tuberous sclerosis
Vitiligo
241
Table 3. Differential Diagnosis of Rash

Rash
History and
symptoms
Target lesions especi- Herpes simplex,

ally on palms or soles Mycoplasma, new
drug
Lesions ranging from Drugssulfa, other
dark red macules
antibiotics, carbawith necrotic centers mazepine, barbituto epidermal detach- rates, allopurinol
ment with prominent
mucosal lesions
Urticaria or swelling
Insect bite, food
of central face,
exposure, drug
respiratory distress
Sunburn-like erythro- Tampon use, nasal
derma, mucosal
packing, wound
hyperemia, strawinfection, barrier
berry tongue,
contraceptive,
desquamation of
influenza
hands & feet (late)
Diffuse petechial erup- Fever, headache,
tion evolving to
nausea, vomiting,
palpable purpura with myalgia, closegray necrotic centers quartered living
conditions,
splenectomy
Subtle evidence of
Fever, hypotension,
soft tissue infection
pain out of propor(pain, swelling,
tion to exam, rapid
warmth), bullae,
progression
necrotizing fasciitis
Centripetally spreading Travel or residence
macular papular
in endemic area,
rash evolving to
tick bite, fever,
petechial purpuric
malaise, headache,
rash
myalgias, vomiting
Palpable purpura
Evidence of systemic involvement:
abdominal pain,
arthritis, epistaxis,
iritis, nephritis,
peripheral neuropathy, pulmonary
hemorrhage
242
Diagnosis
Erythema multiforme
Stevens-Johnson
syndrome, toxic
epidermal
necrolysis
Urticaria, angioedema
Staphylococcal toxic
shock syndrome
Meningococcal
disease
Streptococcal toxic
shock syndrome
Rocky Mountain
spotted fever
Vasculitis
I SIGNS & SYMPTOMS

Table 3 (continued)
Rash
History and
symptoms
Diagnosis
Painful red plaques
Fever, URI, hematologic malignancy
Diffuse sterile
pustules
Steroid use or
taper, NSAIDs,
-hemolytic streptococcus infection,
viral URI, fever,
adenopathy
Pain or pruritus in
Herpes zoster
a dermatomal
distribution
Grouped vesicles on
an erythematous
base in a dermatomal distribution
Sweet syndrome
(acute febrile
neutrophilic
dermatosis)
Generalized pustular
psoriasis
URI, upper respiratory tract infection.
TEST ORDERING
Rash-Specific Testing
Skin biopsy for hematoxylin-eosin sections, immunofluorescence, and electron microscopy to support or rule out a
diagnosis (clinicopathologic correlate often required)
Cultures of infected lesions to direct antibiotic therapy
Other Tests May Be Dictated by an Underlying Illness
Cutaneous findings, associated disease, and tests to consider are listed in Table 4.
INITIAL MANAGEMENT
Urticaria or Angioedema (Drug, Food, Insect Bite)
ABCs
For severe cases
Large-bore IV access with 0.9% normal saline
Diphenhydramine
Famotidine
243
Methylprednisolone
Epinephrine
Followed by diphenhydramine or hydroxyzine
Short course of prednisone
In less severe cases, diphenhydramine or hydroxyzine 50
mg every 4 hours may be enough
Discontinue or avoid any identifiable triggers
Epinephrine (EpiPen) education
Table 4. Tests Dictated by Cutaneous Finding and

Associated Disease
Cutaneous
finding
Aphthous ulcers
Caf au lait spots,

neurofibromas
Dermatitis herpetiformis
Erythema marginatum
Erythema migrans
Erythema nodosum
Gottron papules,
heliotrope rash
244
Associated disease
Tests to consider
Crohn disease,
gluten-sensitive
enteropathy,
Behet syndrome
Neurofibromatosis
Colonoscopy, smallbowel biopsy
Gluten-sensitive
enteropathy
Genetic testing
Serum IgA endomysial

antibody, antigliadin
antibodies, smallbowel biopsy
Rheumatic fever
Throat culture, streptococcal antibody titer,
ESR, ECG, Echo
Lyme disease
ELISA/Western blot
4-6 weeks after
infection
Strep pharyngitis,
Throat culture, ACE
sarcoidosis, inflam- level, serum calcium,
matory bowel
CXR, colonoscopy,
disease, Behet
fungal stains, cultures,
syndrome, histoantigen detection,
plasmosis, coccidi- serologic tests for
oidomycosis
fungal-specific
antibodies
Dermatomyositis
Plasma CK, LDH,
AST/ALT, aldolase,
ANA, anti-Jo-1 antibody, EMG, muscle
biopsy
I SIGNS & SYMPTOMS

Table 4 (continued)
Cutaneous
finding
Associated disease
Tests to consider
Livedo reticularis
Thromboembolic
Platelet count, D-dimer
events, vasculitis,
fibrin degradation
connective tissue
products, peripheral
disorders, pancrea- smear, PT, aPTT,
titis, syphilis, TB
Echo, amylase, lipase,
PPD, AFB smear,
CXR (also see tests for
dermatomyositis,
syphilis, & vasculitis)
Malar rash
Lupus erythemato- ANA, dsDNA, Sm
sus
Palpable purpura
Churg-Strauss syn- CBC, ESR, serum
drome, cryoglobu- complement levels,
linemic vasculitis, serum creatinine,
Henoch-Schnlein BUN, urinalysis,
purpura, microLFTs, hepatitis
scopic polyangiitis, serologic tests, ANA,
Wegener granuloc-ANCA, p-ANCA,
matosis
& cardiac, respiratory, neurologic, &
gastrointestinal tests
Petechial rash
Endocarditis, throm- Blood cultures, Echo,
boembolic events,
platelet count, D-dimer,
thrombocytopenia, fibrin degradation
DIC
products, peripheral
smear, PT, aPTT
Pinch purpura &
Amyloidosis
SPEP/UPEP with
waxy papules
immunofixation,
abdominal wall fat
biopsy, skin lesion
biopsy
Pretibial myxedema Graves disease
TSH, T4
Pyoderma gangreInflammatory bowel CBC, colonoscopy,
nosum
disease, rheumarheumatoid factor,
toid arthritis,
ESR, X-rays,
hematologic malig- LFTs, hepatitis
nancy, chronic
serologic tests
active hepatitis
245
Table 4 (continued)
Cutaneous
finding
Scaling papules,
especially on
palms & soles
Sweet syndrome
(acute febrile
neutrophilic
dermatosis)
Telangiectasia, on
mucosa &
acrally
Painful ulcerative
mucocutaneous
lesions, generalized
rash (often but not
always maculopapular)
Kaposi sarcoma,
molluscum
contagiosum,
severe HSV
Associated disease
Tests to consider
Secondary syphilis
Rapid plasma reagin,

VDRL
Hematologic malig- CBC, skin biopsy,

nancies, solid
preventive cancer
tumors
screening appropriate
for patient age
Rendu-Osler-Weber CBC, CXR, colonossyndrome
copy, CT of head
Primary HIV
infection
HIV
HIV RNA test (viral

load), HIV antibody
test (initially negative
but baseline needed
for later seroconversion)
HIV testing (with
consent), ELISA/
Western blot
ACE, angiotensin-converting enzyme; AFB, acid-fast bacillus; ANA, antinuclear antibody; ANCA, antineutrophil cytoplasmic antibody (c-, cytoplasmic; p-, perinuclear); CXR, chest radiography; DIC, disseminated intravascular coagulation; dsDNA, double-stranded DNA; Echo, echocardiography;
HSV, herpes simplex virus; LFT, liver function test; RF, rheumatoid factor;
RPR, rapid plasma reagin; SPEP, serum protein electrophoresis; Strep,
streptococcal; T4, thyroxine; TSH, thyroid-stimulating hormone; UPEP,
urine protein electrophoresis.
Drug Eruption (Exanthem, Stevens-Johnson Syndrome,

Toxic Epidermal Necrolysis)
ABCs
Obtain a complete drug historyprescription, nonprescription, topical, ophthalmic.
Identify and discontinue or find substitutes for likely culpritsantibiotics, anticonvulsants, NSAIDs, angiotensinconverting enzyme inhibitors, thiazide diuretics, dyes.
246
I SIGNS & SYMPTOMS
Measure drug levels.

Rash may worsen for several days despite stopping the inciting agent.
If mild, treat symptomatically (e.g., antihistamines, topical
corticosteroids).
If blistering and exfoliation, administer fluids and use aseptic technique.
If signs of infection, culture and give broad-spectrum antibiotics.
If eye is involved, request ophthalmology consult.
Skin biopsy
Patient education to avoid recurrence
After a severe reaction, never rechallenge a patient with drug
or skin testing.
Rocky Mountain Spotted Fever

ABCs
Diagnosis is made on basis of the clinical and epidemiologic features.
Doxycycline
Supportive therapy
Remain alert for mental status changes, renal dysfunction,
myocarditis, and respiratory failure.
Common but nonspecific changes in lab values: leukopenia,
thrombocytopenia, hyponatremia, elevated ALT and AST
levels
Antibody serologic tests will not be positive for 7-10 days
after symptom onset.
Staphylococcal Toxic Shock Syndrome

ABCs
Vancomycin (until penicillin and oxacillin sensitivities known)
Removal of tampons, packings, dressings
Surgical exploration and debridement if indicated
Clindamycin 900 mg every 8 hours IV may be added to
reduce toxin production
IV immunoglobulin 0.5 g/kg daily IV 4 days may neutralize circulating toxins
247
Streptococcal Toxic Shock Syndrome

ABCs
Ceftriaxone + clindamycin 900 mg every 8 hours IV
Aggressive supportive care
Surgical exploration and debridement are most important.
Tissue (intraoperative) cultures and sensitivities
IV immunoglobulin 0.5 g/kg daily 4 days may neutralize
circulating toxins.
Meningococcal Meningitis
ABCs
Gram stain, culture, and susceptibilities performed on
Blood
CSF
Skin biopsy (may be positive even after initiation of antibiotic therapy)
Bacterial antigen testing on CSF
Ceftriaxone
Bullous Pemphigoid
Oral corticosteroids to achieve remission
After remission, reduce prednisone dose to half and then
slowly taper
Steroid-sparing drugs may be tried (e.g., azathioprine, dapsone, methotrexate)
In mild casesdapsone may be adequate
For localized mild cases, topical corticosteroids may suffice.
Aseptic technique
Antibiotic coverage as indicated by severity or signs of
infection
248
I SIGNS & SYMPTOMS

SPLENOMEGALY
Thomas M. Habermann, M.D.

Splenic rupture
An uncommon cause of splenomegaly
Caused by penetrating or nonpenetrating trauma or may be
spontaneous
Requires immediate, emergent treatment
Presentation of splenic rupture may be delayed 24-48
hours after trauma.
Systemic illnesses predisposing to traumatic splenic rupture
Myeloproliferative and lymphoproliferative disorders
Endocarditis
Infection: TB, brucellosis, cytomegalovirus, Epstein-Barr
virus, HIV, viral hepatitis, histoplasmosis, toxoplasmosis, malaria
ADDRESSING THE RISK (ACUTE VS. CHRONIC)
Splenic rupture
History reveals abdominal pain that may be referred to
left shoulder (diaphragm irritation).
Physical exam may show orthostasis, peritoneal signs, or
hypotension.
If splenic rupture is suspected, rapid assessment with abdominal CT and collaboration with a surgical team are essential.
The differential diagnosis for splenomegaly is listed in Table 1.
The causes of splenomegaly
Work hypertrophy from immune response or RBC destruction
Congestive
Myeloproliferative
Infiltrative (nonneoplastic and neoplastic)
249
Table 1. Differential Diagnosis for Splenomegaly

Work hypertrophy
Immune response
Bacterial infectionTB, subacute bacterial endocarditis
Viral infectioncytomegalovirus, Epstein-Barr virus,
HIV, viral hepatitis
Fungal infectionhistoplasmosis
Parasitic infectiontoxoplasmosis, malaria
Felty syndrome
Serum sickness
RBC destruction
Thalassemia major
Pyruvate kinase deficiency
Hemolytic diseases
Congestive
Cirrhosis & portal hypertension
Portal, hepatic, or splenic vein thrombosis
Myeloproliferative
Chronic myelogenous leukemia
Extramedullary hematopoiesismyeloid metaplasia from
myelofibrosis, marrow damage by toxins, radiation, infiltration by tumor or leukemia
Polycythemia vera
Lymphoproliferative
Lymphoma
Chronic lymphocytic leukemia
Acute lymphocytic leukemia
Hairy cell leukemia
Infiltrative
Nonneoplasticsarcoidosis, amyloidosis, Gaucher disease
Neoplasticacute nonlymphocytic leukemia, metastatic tumor
Other
Trauma
Splenic cyst(s)
Pyogenic abscess
Hemangioma
Idiopathic splenomegaly
250
I SIGNS & SYMPTOMS

History of Present Illness
Acute vs. chronic disease
Abrupt onset of symptoms suggests a traumatic, infectious, or inflammatory cause.
Chronic history of constitutional complaints suggests a
neoplastic cause.
Characteristics of the symptoms
Fatigue and malaisecommon symptoms in acute and
chronic liver disease, hematologic malignancy, and chronic systemic infection
Anorexiacommon symptom in acute and chronic liver
disease, weight loss, hematologic malignancy
Persistent dull ache or fullness in left upper quadrant
moderate-massive splenomegaly (may be accompanied
with early satiety)
Differential diagnosis is of massive splenomegaly:
myeloproliferative disorders, non-Hodgkin lymphoma,
hairy cell leukemia, splenic cyst, Gaucher disease.
Increase in abdominal girthsuggestive of ascites and
advanced chronic liver disease, hepatic malignancy, venous
outflow obstruction
Prurituslymphoma, cholestasis
Urticariahepatitis B infection (with synovitis), immune
complex disease (with petechiae), lymphoma
Pharyngitis, rash, and lymphadenopathyEpstein-Barr
virus or cytomegalovirus
History of congestive heart failure or cirrhosiscongestive disease
Family History
Genetic anemic diseasessickle cell anemia (SS, SC), thalassemia major or minor, hereditary spherocytosis
Genetic associationalcoholic liver disease
Social History
Promiscuous sexual activity, illicit drug use (endocarditis if IV
drugs), or history of blood transfusionviral hepatitis, HIV
251
Exposure to a marrow-toxic medication or environmental

toxin, including heavy use of ethanol.
Physical Exam
Evaluate for lymphadenopathy.
Perform a thorough cardiac and liver exam to look for signs
of dysfunction, infection or inflammation, and portal hypertension
Exam of the spleen should involve percussion and palpation.
Normal spleen is not palpable in adults.
Tenderness suggests peritoneal inflammation from infection, infarction, or rapid enlargement.
ORDERING TESTS
Lab Tests
Initial laboratory evaluation of splenomegaly includes a
CBC, with differential and platelet count, and peripheral
blood smear (Tables 2 and 3).
Perform liver tests to evaluate for hepatic abnormality and
measure bilirubin as an index of cholestasis or hemolysis.
Radiographic Evaluation
CT with IV contrast/MRI
Useful for evaluating parenchymal splenic disease
CT can accurately assess size.
CT may demonstrate lymphadenopathy in deeper nodal
groups and is especially useful for suspected lymphoma.
CT can identify tumors and small lacerations not detected by other imaging methods.
MRI allows visualization of vessels without IV contrast,
but is occasionally used for this purpose.
Tissue Biopsy
Bone marrow aspiration is indicated for evaluation of hematologic disorders and infectious disease.
Allows cytologic and histologic exam of bone marrow
cells
Specimen may provide information about infection
through culture and staining (acid-fast bacilli, yeast,
fungus).
252
I SIGNS & SYMPTOMS

Table 2. Initial Evaluation of Splenomegaly: CBC With
Differential and Platelet Count
Anemia
Microcytic: thalassemia, hereditary sideroblastic anemia
Macrocytic: polychromasia (check reticulocyte count), myeloid
metaplasia, target cells (thalassemia; hemoglobins C, D, E, S;
liver disease), spherocytosis
Normocytic: acute blood loss, splenic rupture, bone marrow
infiltration (lymphoma, myeloproliferative diseases)
Erythrocytosis
Polycythemia vera
Secondary polycythemia
Hypoxic erythrocytosis: pulmonary disease, chronic cor
pulmonale
Hemoglobinopathies
Leukopenia
Myelodysplastic disease
Hypersplenism: congestive disease, malaria, sarcoidosis
Infection: mononucleosis, HIV, overwhelming bacterial infection
Felty syndrome
Leukocytosis
Neutrophilic
Acute bacterial infections
Lymphocytosis
High (15 109/L cells): infectious mononucleosis
(atypical lymphocytes), acute & chronic lymphocytic
leukemia
Moderate (<15 109/L cells): viral infections
(infectious mononucleosis, hepatitis, cytomegalovirus, HIV), toxoplasmosis, neoplasm (carcinoma,
Hodgkin disease)
Eosinophilic
Hypersensitivity reaction
Neoplasm: Hodgkin and non-Hodgkin lymphoma
Basophilic
Myeloproliferative disorder
Monocytosis
Subacute bacterial endocarditis
Chronic infection: TB, malaria
253
Table 2 (continued)
Thrombocytopenia
Lymphoma
Aplastic anemia
Marrow damagechemicals, ionizing radiation, alcohol,
infection, leukemias, metastatic disease, myelofibrosis
Increased destruction of plateletschronic lymphocytic
leukemia, lymphoma, systemic lupus erythematosus
Infectioninfectious mononucleosis, cytomegalovirus, HIV,
malaria, sepsis
Thrombocytopeniaidioipathic or secondary
Thrombocytosis
Primary
Polycythemia vera
Chronic myelocytic leukemia
Myelofibrosis
Secondary
Infection
Inflammatory disease
Neoplasm
Asplenia
Postsurgical procedure
Lymph node biopsy is indicated for patients with persistent,

unexplained, localized or generalized lymphadenopathy >1
cm and persisting more than 1 month.
Diagnostic laparotomy with splenectomy may be indicated
after complete diagnostic evaluation does not disclose a cause
of splenomegaly and primary splenic lymphoma is suspected.
MANAGEMENT
Work Hypertrophy
Immune response
Bacterial endocarditisblood cultures, echocardiogram,
empiric antibiotic treatment to cover Staphylococcus,
Streptococcus, and Enterococcus while culture results are
pending
Infectious mononucleosis
Primarily Epstein-Barr virus but may be cytomegalovirus
254
I SIGNS & SYMPTOMS

Table 3. Initial Evaluation of Splenomegaly: Peripheral
Blood Smear
Feature
Target cells
Basophilic stripping
Schistocytes (fragmented
RBCs)
Teardrop cells
Spherocytes
Sickle cells
Acanthocytes
Bite cells
Howell-Jolly bodies
Intraerythrocytic parasite
Condition
Thalassemia
Hemoglobins C, E, SC
Liver disease
Splenectomy
Hemolysis
Lead poisoning
Thalassemia
Thrombotic thrombocytopenic
purpura
Vasculitis
Myelofibrosis
Myelophthisis
Autoimmune hemolytic anemia
Burns
Clostridium infections
Sickle cell anemia (hemoglobin SS,
SC)
Hemoglobin S -thalassemia
Chronic or severe liver disease
Unstable hemoglobinopathy
Postsplenectomy
Acquired hyposplenism
Malaria
No treatment available other than symptomatic treatment with acetaminophen or NSAIDs.

For thrombocytopenia, autoimmune hemolytic anemia,
or airway obstructive lymphoid tissue, a course of corticosteroids may be beneficial.
Vigorous activity is avoided for 1 month or until
splenomegaly regresses.
255
RBC Destruction
Sickle cell anemia
Hydration and oxygen treatment if patient is hypoxic
Folic acid supplementation and transfusion for hemolytic and aplastic crises
Patient may be functionally asplenic and require vaccination against encapsulated organisms.
Hemolytic anemia
CBC with peripheral smear and reticulocyte count
For hereditary membrane defect, hemoglobin <8.0 g/dL,
and reticulocyte count >11%, splenectomy may be
indicated.
Autoimmune hemolytic anemia is confirmed with a direct
Coombs test and immunosuppressive therapy instituted
dependent on the disease.
Intravascular hemolysis treatment is directed at the underlying disorder.
Folate supplementation and iron replacement may be necessary for patients with valve hemolysis.
Acute intravascular hemolysis, disseminated intravascular coagulation, or acute renal failure may require transfusion support or hemodialysis.
Congestive
Cirrhosis and portal hypertension
Doppler ultrasonography to assess patency of blood vessels and direction of flow
Treat underlying disease.
Consider shunt surgery or percutaneous placement of a
shunt.
Watch for signs of hepatic encephalopathy or intestinal
ischemia if thrombus involves the portal or hepatic veins.
Congestive heart failurelow salt diet, diuretics (spironolactone), angiotensin-converting enzyme inhibitor, -blocker, digitalis
Infiltrative
Nonneoplastic
Sarcoidosisdiagnosed with chest X-ray for staging and
biopsy of easily accessible sites; treatment with corticosteroid if clinically indicated
256
I SIGNS & SYMPTOMS

Amyloidosisdiagnosed with clinical suspicion, fat aspiration, and protein electrophoresis
Gaucher diseasetreatment with synthetic glucocerebrosidase and symptomatic treatment, including blood
transfusions for anemia and partial splenectomy for severe
cardiopulmonary compromise or hypersplenism
Neoplastic
Lymphoma, acute and chronic lymphocytic leukemia,
hairy cell leukemia, metastatic tumor
Treat underlying disease
257
I SIGNS & SYMPTOMS

THROMBOCYTOPENIA

Active bleeding (i.e., gastrointestinal tract bleed) in patient
with thrombocytopenia can lead to life-threatening
hemorrhage.
Platelet counts <10 109/L are associated with spontaneous
intracerebral hemorrhage and require immediate evaluation.
Heparin-induced thrombocytopenia (HIT) activates platelets
and is associated with potentially life-threatening thrombosis (myocardial infarction, cerebrovascular accident, deep
venous thrombosis or pulmonary embolism, arterial thrombosis)
Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are life-threatening conditions
that cause thrombocytopenia and hemolytic anemia requiring immediate hospitalization and plasma exchange.
Disseminated intravascular coagulation can be a life-threatening complication of tissue injury that leads to thrombosis
or hemorrhage.
ADDRESSING THE RISK
In Hemorrhaging Patient
Obtain IV access, and prepare for immediate platelet
transfusion
Immediate hematology consult
Check PT and PTT to identify any coexisting coagulopathy
Be mindful of possible coexistent qualitative platelet defect
due to NSAID use, uremia, alcoholism, cirrhosis, myeloma,
Special abbreviations used in this chapter: HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; ITP, idiopathic thrombocytopenic
purpura; TTP, thrombotic thrombocytopenic purpura.
259
Waldenstrm macroglobulinemia or myeloproliferative

disorders.
Avoid invasive procedures (central catheter at noncompressible site, lumbar puncture, nasogastric tube, or surgery)
in patients with platelet counts <50 109/L until platelet
deficit is corrected.
In Patient With Possible HUS or TTP

Request immediate hematology consult.
Prepare for possible plasma exchange.
In Patient With Possible HIT

Stop all heparin (including line flushes).
Consider alternative anticoagulant (lepirudin, danaparoid,
argatroban).
Consult hematology.
Rule out spurious thrombocytopenia due to platelet clumping. This can be done by reviewing the smear and drawing
a repeat platelet count in a citrated tube.
The two main causes of thrombocytopenia are production
failure or destruction (Tables 1 and 2). Other causes are
sequestration (Table 3) and dilution. Platelets are diluted
by massive RBC transfusions.
Table 1. Decreased Platelet Production

Nutritional deficiencies:* vitamin B12, folate
Aplastic marrow, usually pancytopenic
Myelodysplastic syndromes or leukemia
Toxin-mediated marrow suppression: alcohol, drugs
Cirrhosis
Sepsis
Medications: H2-blockers, proton pump inhibitors, thiazide
diuretics, many others
Viral infection: Epstein-Barr virus, HIV, hepatitis C, mumps
Myelophthisis
Congenital platelet deficiencies
*The decrease usually is moderate but can be severe.
260
I SIGNS & SYMPTOMS

Table 2. Destruction or Consumption of Platelets
Immune-mediated
Mechanical, consumption
Idiopathic thrombocytopenic
purpura
coagulation
Heparin-induced thrombocyto- Hemolytic uremic syndrome,
penia
thrombotic thrombocytopenic
Treatment-induced: quinine,
purpura
quinidine, valproic acid
HELLP (hemolysis, elevated liver
Evans syndrome
enzymes, low platelet count)
syndrome, seen in pregnancy
Endocarditis
Prosthetic cardiac valves
Infection: Rickettsia or ehrlichiosis
Antiphospholipid antibody
syndrome
Vasculitis
Table 3. Sequestration of Platelets

Splenomegalycommon causes include the following:
chronic myelogenous leukemia, polycythemia vera,
agnogenic myeloid metaplasia, lymphoma, Hodgkin disease,
Mycobacterium avium complex, cirrhosis with portal
hypertension, TB, malaria, histoplasmosis, endocarditis,
autoimmune hemolysis

General Principles
If thrombocytopenia began after admission to hospital, focus
evaluation on new medications, HIT, or disseminated intravascular coagulation as cause of thrombocytopenia.
If patient presents to hospital with thrombocytopenia, consider idiopathic thrombocytopenic purpura (ITP), HUS or
TTP, acute leukemia, or HIV.
An algorithm for thrombocytopenia is shown in Figure 1.
261
262
Thrombocytopenia
Check Hg & WBC count
Pancytopenia
Anemia
Normal Hg & WBCs
Check smear
Not on heparin
On heparin
Schistocytes
Blasts?
No schistocytes
Blasts on smear
Splenomegaly
No splenomegaly
Sequestration
ITP, DIC, HIV, MDS,

therapy-induced
Evaluate causes
of splenomegaly
Check smear for blasts

Check labs for DIC
Check for HIV
Review medications
Consider HIT
HUS, TTP
DIC
Endocarditis
No: vitamin B12 or

folate deficiency
or Evans syndrome
Yes: leukemia or
MDS
No: ethanol, toxin, medication,
infection (HIV, EBV, CMV, HCV),
marrow aplasia, myelophthises,
sarcoidosis, SLE, amyloidosis,
vitamin B12 or folate deficiency
Stop all heparin

Check HIT antibody
Consider alternative
anticoagulant
Check labs for DIC
Blood culture
Start plasma exchange
Bone marrow biopsy
with chromosome analysis
Review medications, check

vitamin B12 & folate
Check TSH, HIV
Bone marrow biopsy
Fig. 1. Algorithm for thrombocytopenia. CMV, cytomegalovirus; DIC, disseminated intravascular coagulation; EBV, Epstein-Barr virus; HCV, hepatitis C
virus; Hg, hemoglobin; HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; ITP, idiopathic thrombocytopenic purpura; MDS,
myelodysplastic syndrome; SLE, systemic lupus erythematosus; TSH, thyroid-stimulating hormone; TTP, thrombotic thrombocytopenic purpura.
I SIGNS & SYMPTOMS

History
Personal history or family history of bleeding disorder (i.e.,
uncontrolled bleeding with dental procedures or previous
surgical procedures)
Menorrhagia?
New medications: thiazide, H -blocker, quinidine, proton
2
pump inhibitor, valproic acid, quinine, sulfa, gold?
Recent viral illness (associated with ITP, aplastic anemia)?
Diarrhea or gastrointestinal symptoms (associated with
HUS)?
Headache, confusion, somnolence? Consider intracranial
bleed if platelets <10 109/L.
Identify the neurologic symptoms of TTP.
NSAID use? Identify coexistent qualitative platelet defect.
Is patient on heparin? Consider HIT.
Pregnant or recent delivery? Consider HELLP syndrome.
Physical Exam
Petechiae
Purpura (mucous membrane purpura = wet purpura)
Bruising, ecchymosis
Neurologic exam with focal deficit
Ophthalmoscopic exam
Stool guaiac
Lymphadenopathy or splenomegaly
SPECIFIC THROMBOCYTOPENIC CONDITIONS

Disseminated Intravascular Coagulation
A systemic thrombotic state triggered by tissue injury and
leading to intravascular thrombosis and consumption of clotting factors
Patients become coagulopathic secondary to consumption
of coagulation factors and may subsequently bleed.
Diagnosis is suggested clinically by diffuse oozing or overt
hemorrhage at surgical sites and line sites.
Patient may have simultaneous evidence of thrombosis (skin
necrosis, digital ischemia, deep venous thrombosis, myocardial infarction) and bleeding.
263
Presence of soluble fibrin monomers is the most specific lab

finding.
Lab findings of increased INR, increased PTT, and positive
D-dimer support the diagnosis.
Peripheral blood smear may or may not show schistocytes.
Four principle underlying causes of disseminated intravascular coagulation
Sepsis, infection
Tissue injury: ischemia, trauma, pancreatitis
Malignancy
Obstetric complications
HUS or TTP
HUS or TTP is an inflammatory state characterized by
endothelial injury leading to formation of microthrombi and
fibrin strands in small blood vessels.
Pathophysiologythought to be a deficiency or absence
of metalloprotease enzymes that cleave von Willebrand
factor. Without these cleaving enzymes, large von
Willebrand multimers accumulate, leading to endothelial
injury that initiates thrombosis.
HUS or TTP causes thrombocytopenia secondary to
platelet consumption and anemia secondary to fragmentation of erythrocytes by fibrin strands in microvasculature.
Majority of patients with TTP do not have the full clinical pentad: fever, thrombocytopenia, microangiopathic
hemolytic anemia, renal disease (ranging from microscopic hematuria to acute renal failure), and neurologic
symptoms (headache, confusion, seizure).
Only requirements for the diagnosis and the only requirements to initiate empiric treatment (plasma exchange)
while work-up is pursued: microangiopathic hemolytic
anemia and thrombocytopenia
Without plasma exchange, mortality approaches 90%, but
with treatment it is reduced to 20%-25%.
HUS is associated with E. coli O157:H7 infection.
TTP can be idiopathic, medication-induced (clopidogrel,
ticlopidine, mitomycin C), or hereditary.
HIT
Two types of HIT
264
I SIGNS & SYMPTOMS

Type I
Benign
Characterized by mild decrease (20%-30%) in platelet
count caused by platelet agglutination that typically
occurs within first 48 hours after heparin exposure
Occurs in 20% of patients exposed to heparin
No important clinical sequellae of type I HIT
Does not require cessation of heparin therapy
Type II
Caused by immune-mediated platelet destruction due to
heparin exposure
Pathophysiologythought to be secondary to immunemediated consumption of platelets due to IgG antibody
that reacts to heparin bound to platelet factor 4 antigen.
In addition to causing platelet destruction, antibodies
activate platelets, leading to major thrombotic (80%
venous, 20% arterial) complications. This immune-mediated reaction occurs in 1% of persons exposed to heparin.
Type II HIT typically occurs after 4-5 days of heparin
exposure but can occur in <12 hours if person was
exposed to heparin in the last 100 days.
HIT is a clinical diagnosis based on thrombocytopenia developing after exposure to heparin.
Characterized by a 50% decrease or >100 109/L decrease
in platelets
Lab testing (presence of anti-platelet factor 4 antibody)
has good specificity and can support diagnosis of type II
HIT, but low sensitivity and long processing time make
HIT a clinical diagnosis.
ITP
Diagnosis of exclusion and can be made only after other
causes of thrombocytopenia (problems with production,
destruction, or sequestration) have been excluded.
Causeanti-platelet antibodies leading to immune-mediated
platelet destruction.
Anti-platelet antibody testing has poor sensitivity and specificity and is not indicated in the work-up or diagnosis of ITP.
265
Rule out HIV in patients with risk factors.

Bone marrow biopsy should be performed before ITP is
diagnosed in patients older than 60 and in younger patients
if the diagnosis is unclear.
TESTS AND WORK-UP

Everyone
CBC with differential count (note: automated platelet count
is inaccurate if count is <10 109/L)
Blood smearcritical component of work-up of thrombocytopenia
Rule out platelet clumping.
Schistocytes indicate TTP or HUS, disseminated intravascular coagulation, or endocarditis
Blasts indicate acute leukemia or myelodysplastic syndrome; next step is order bone marrow biopsy
Creatininemay be increased in HUS or TTP
Urinalysismicroscopic hematuria in HUS or TTP
Febrile?
Consider HUS/TTP, subacute bacterial endocarditis, disseminated intravascular coagulation
Blood culture to identify possible endocarditis
PT, PTT, D-dimer, soluble fibrin monomers to identify disseminated intravascular coagulation
Consider echocardiography if new murmur or risk factors
for endocarditis.
Stool culture for E. coli O157:H7
Other
Possible ITP
Check HIV test.
Bone marrow biopsy in patients older than 60
Neurologic symptoms
CT of head to rule out intracranial bleed
Consider TTP.
Blasts on peripheral smearbone marrow biopsy
On heparintest for HIT antibody.
Other considerationsvitamin B
12, folate, thyroid-stimulating hormone (rarely cause platelets <50,000 by themselves)
Unclear causebone marrow biopsy
266
I SIGNS & SYMPTOMS

MANAGEMENT
General
Risk of bleeding or hemorrhage with surgery or trauma
increases with platelets <50-100 109/L.
Avoid invasive procedures until platelet count is corrected.
Transfusion thresholds
Platelets <10 109/LTransfuse platelets in all patients,
with possible exception of ITP (see ITP below).
Bleeding patientTransfuse platelet count to >50 109/L.
Preoperative
General surgeryTransfuse platelet count to >50
109/L.
Neurosurgery or ophthalmologic surgeryTransfuse
platelet count to >100 109/L.
Disseminated Intravascular Coagulation
Supportive care
Identify and treat underlying cause.
Most authorities believe transfusing platelets and fresh frozen
plasma fuels the fire by enhancing cytokine cascade: avoid
transfusion unless active hemorrhage.
In refractory disseminated intravascular coagulation with
thrombotic or hemorrhagic complications, some hematologists begin heparin therapy while simultaneously giving fresh
frozen plasma. The intent of this counterintuitive approach
is to use heparin to arrest the prothrombotic state while simultaneously replacing depleted coagulation factors to prevent
hemorrhage. This approach requires technical expertise and
experience in treating disseminated intravascular coagulation and should be initiated under the direction of a hematologist.
HUS or TTP
Stop clopidogrel and ticlopidine.
Stop nephrotoxic medications.
Hydrate
Prepare for immediate plasma exchange (consult hematology and nephrology).
267
If no plasma exchange at your center, give 4 units fresh

frozen plasma, and arrange for immediate transfer.
Microangiopathic hemolytic anemia (i.e., schistocytes on
peripheral blood smear) and thrombocytopenia are only
requirements to initiate plasma exchange while work-up is
pursued.
Value of adding corticosteroids to plasma exchange is debated but usually recommended initially (IV methylprednisolone).
Follow daily LDH and platelet counts while patient has plasma exchange.
Generally, patients receive daily plasma exchange until
platelets >150 109/L and LDH is normal and then can be
considered for tapering of frequency of plasma exchange.
HIT
Stop all heparin (including line flushes).
Do not convert to low-molecular-weight heparin (20%-30%
cross-reactivity of antibodies).
Evaluate for symptoms or physical exam findings of arterial (myocardial infarction, cerebrovascular accident) or venous
(deep venous thrombosis, pulmonary embolism) thrombosis.
Test for HIT antibody (ELISA-based anti-platelet factor 4
antibody).
Studies suggest discontinuation of heparin alone may not
be adequate to decrease risk of thrombosis and recommend
alternative anticoagulation for all patients with HITeven
those without thrombosis at time of diagnosis.
Consult hematology for other options for anticoagulation
(i.e., lepirudin, argatroban, danaparoid).
ITP
Start prednisone, 1 mg/kg
Patients with ITP generally respond poorly to platelet transfusions, and their remaining platelets are large and hyperfunctional.
General principleAvoid platelet transfusions in ITP patients.
Splenectomy for refractory ITP
IV immunoglobulin or anti-D immunoglobulin (Whinrho)
can be used to temporarily maintain platelet count before
splenectomy.
Consult hematology.
268
I SIGNS & SYMPTOMS

Splenomegaly
Identify the cause.
Most common cause varies by population studied.
For patients at risk for HIV, Mycobacterium avium complex, TB, or other infection is most likely cause.
In general population, chronic myelogenous leukemia,
lymphoma, polycythemia vera/myeloproliferative disorder, or cirrhosis with portal hypertension is most likely
cause.
In immigrants, consider malaria, TB, leishmaniasis.
Role of splenectomy for treatment depends on underlying
process and severity of thrombocytopenia.
Consult hematology if splenectomy is considered.
269
I SIGNS & SYMPTOMS

TREMOR AND MOVEMENT
DISORDERS
Matthew L. Flaherty, M.D.
Andrea C. Adams, M.D.
The most common causes of tremor and movement disorder
(including ataxia in this chapter) usually are not acutely life
threatening. However, several less common conditions may
be rapidly fatal or debilitating and should be considered.
Three Disorders of Neuromuscular Rigidity
Neuroleptic Malignant Syndrome
Idiosyncratically induced by dopamine blockers, including
neuroleptics (antipsychotics) and antiemetics (e.g., promethazine)
Characteristicsmuscular rigidity, involuntary movement,
unstable blood pressure, decreased mental status, fever
Mortality up to 30%
Malignant Hyperthermia
Disorder of excessive muscle contraction leading to hyperthermia, most often associated with succinylcholine and
halothane anesthesia
Responsible gene defect is often familial
Tetanus
Caused by wound contamination with Clostridium tetani,
which produces the neurotoxin tetanospasmin
Occurs in unimmunized or underimmunized person
Typical incubation period: 7-21 days (range, 5 days-15
weeks)
Often begins with stiff jaw (trismus), stiff neck, dysphagia,
and irritability
Progresses to generalized rigidity and muscle spasms
triggered by minor stimuli
271
Three Causes of Ataxia

Cerebellar Hemorrhage
Acute onset of ataxia (particularly gait), often with headache, vertigo, vomiting, decreased mental status, variable ocular signs
(including ipsilateral cranial nerve VI palsy), nuchal rigidity
Excessive intracranial pressure may cause brainstem compression and death.
Wernicke Encephalopathy
Classic triad: gait ataxia, ophthalmoplegia, confusion
Nystagmus is often present
Associated with alcoholism, caused by thiamine deficiency
If inadequately treated, may progress to chronic amnestic
state, Korsakoff psychosis
Death is usually due to associated illnesses (e.g., hepatic
failure, infection)
Drug Toxicity
Phenytoin, carbamazepine, valproic acid, lithium, alcohol,
benzodiazepines, other sedatives
Overdose may lead to hemodynamic instability, pulmonary
insufficiency, seizures, or dangerous falls
Two Causes of Tremor

Drug Toxicity
Lithium, valproic acid, stimulants (including cocaine and
amphetamine)
Classically produces action tremor, which increases as
outstretched hand approaches a target
Drug Withdrawal
Remember the 3 Bs of fatal withdrawal: booze (ethanol),
benzodiazepines, barbiturates.
Consider hepatic encephalopathy as cause of decreased mental status and movement disorder (especially asterixis) because
benzodiazepines make the condition of these patients worse.
ADDRESSING THE RISK

Pay attention to airway, breathing, and circulation and general
medical management. Patients with above conditions often
require monitoring in ICU.
272
I SIGNS & SYMPTOMS

Specific Management Points
Neuroleptic Malignant Syndrome
Withdraw dopamine blockers, lithium, anticholinergics.
Use antipyretics and cooling as necessary.
Monitor serum electrolytes (potassium, calcium, phosphorus),
renal function, urine output, CK levels, acid-base balance
(remember to correct arterial blood gas values for temperature), and CBC.
Causes of deathrenal failure, electrolyte imbalance with
arrhythmia, coagulopathy, others
Pharmacologic treatment with bromocriptine or dantrolene
Malignant Hyperthermia
Monitor as for neuroleptic malignant syndrome.
Treat with dantrolene.
Anesthesiologists are usually familiar with diagnosis and
treatment.
Tetanus
Tetanus immune globulin, 500 units IM, followed by tetanus
toxoid immunization at a different site
Consider surgical debridement of causative wounds.
Use penicillin, metronidazole, or other antibiotic appropriate
for Clostridium infection.
Mild sedation with benzodiazepines to reduce spasms
Assess respiratory status frequently; mechanical ventilation
may be needed.
Cerebellar Hemorrhage
If concerned about cerebellar hemorrhage, CT of head
If hemorrhage is confirmed, urgent neurosurgical consultation (decompression can be life saving)
Wernicke Encephalopathy
Immediate treatmentthiamine, 50-100 mg IV immediately
+ 50 mg PO/IM per day for 3 days
Provide balanced diet and multivitamin.
Always administer thiamine when giving glucose to
273
alcoholics or poorly nourished persons because glucose alone

may precipitate Wernicke encephalopathy.
Drug Toxicity
Check drug levels if availableethanol, phenytoin, carbamazepine, valproic acid, lithium.
Consult poison control or emergency department physician
for overdose management.
Drug Withdrawal
Monitor vital signs, agitation level, mental status.
Standardized rating scales (often performed by nursing at
frequent intervals) are useful.
Treatment
Benzodiazepine taper (usually lorazepam or chlordiazepoxide) for ethanol and benzodiazepine withdrawal
Barbiturates (usually pentobarbital or phenobarbital) for
barbiturate withdrawal
Definitions
Akathisiasubjective feeling of motor restlessness, classically produced by dopamine blockers (e.g., antipsychotic
and antiemetic medications), sometimes confused with psychotic agitation
Ataxiamuscular incoordination, variously manifested in
limbs, head, trunk, or gait
Athetosisceaseless, slow, involuntary writhing movements,
especially the hands
Ballismusviolent, flinging movements of limbs caused by
contraction of proximal muscles
Choreacontinual, complex, rapid movements that appear
coordinated but are involuntary
Clonusmovement marked by contractions and relaxations of a muscle occurring in rapid succession; typically associated with spasticity and upper motor neuron
damage
Dyskinesiageneral (nonspecific) term for abnormal, involuntary, hyperkinetic movements
Dystoniadyskinetic movements or abnormal postures
caused by disordered muscle tone
274
I SIGNS & SYMPTOMS
Myoclonussudden, shocklike contractions of a muscle or

muscle group causing a focal or generalized jerk
Ticsrapid, stereotyped, patterned movements under partial
voluntary control
Tremorinvoluntary, rhythmic trembling caused by alternating contraction and relaxation of opposing muscle
groups
Action tremortremor most prominent when a limb is
being used (sometimes applied to postural tremor)
Intention tremorusually a description of ataxic limb
movements, thus not a true tremor; as the patients hand
approaches a target, it wavers erratically (failed motor
compensation for inaccuracy)
Postural tremortremor noticeable when a limb is held in
a stationary, usually outstretched, posture
Resting tremortremor most prominent with limb at rest,
often dampens with voluntary limb movement

Conditions associated with tremor, chorea, myoclonus, and
dystonia are listed in Table 1.
Tremor
Parkinson Disease
Classic triad: resting tremor, bradykinesia, rigidity
Often an unsteady, stooped gait with small steps (festinating
gait)
Masked facies, micrographia
Generally responsive to levodopa
Parkinson Plus Syndromes (Progressive Supranuclear
Palsy, Multiple System Atrophy, Others)
Involve parkinsonism and other neurologic deficits
Levodopa is less efficacious than in Parkinson disease
Progressive supranuclear palsyimpaired vertical gaze,
dysarthria, dysphagia
Multiple system atrophy may include autonomic failure,
lower motor neuron signs, ataxia
275
Table 1. Conditions Associated With Tremor, Chorea,

Myoclonus, and Dystonia
Tremor
Chorea
Parkinson disease
Huntington chorea
Parkinsonism
Sydenham chorea
Drugs: dopamine
Chorea gravidarum
antagonists
Senile chorea
Progressive supraCreutzfeldt-Jakob disease
nuclear palsy
Wilson disease
Multiple system atrophy
Stroke
Stroke or other disease
Systemic lupus erythemaof basal ganglia
tosus
Physiologic tremor
Cerebral palsy
Drug-enhanced
Thyrotoxicosis
Caffeine
Polycythemia vera
Theophylline
Hyperosmolar, nonketotic
Prednisone
hyperglycemia
Amphetamine
Lithium
Drugs
Tricyclics
Birth control pills
Other enhancers
Anticonvulsants
Drug withdrawal
Stimulants
Thyrotoxicosis
Anticholinergics
Hypoglycemia
Antidepressants
Pheochromocytoma
Dopamine agonists
Emotion
Dopamine antagonists
Essential tremor
Rigidity
Myoclonus
Neuroleptic malignant
Myoclonic epilepsy
syndrome
Anoxic brain injury
Malignant hyperthermia
Hepatic failure (asterixis is
Tetanus
sometimes described as
Strychnine poisoning
negative myoclonus)
Severe parkinsonism
Uremia
Stiff-person syndrome
Meningitis
Psychiatric illness
Encephalitis
Ballismus
Cephalosporin/penicillin
Subthalamic nucleus
Tics
infarction or injury
Tourette syndrome
Benign habit spasms
276
I SIGNS & SYMPTOMS

Table 1 (continued)
Dystonia
Drugs (often an acute
dystonic reaction)
Dopamine agonists
Antidepressants
(tricyclics, lithium)
Certain antihistamines
Cocaine
Idiopathic (primary dystonias)
Focal dystonias (e.g., torticollis, writers cramp)
Head trauma
Anoxia
Meningitis
AIDS (toxoplasmosis,
progressive multifocal
leukoencephalopathy)
Hereditary/degenerative
disease (Wilson disease,
Parkinson disease,
Huntington disease,
progressive supranuclear
palsy)
Ataxia (acute or subacute onset)

Cerebellar infarction or
hemorrhage
Brainstem infarction or
hemorrhage
Hydrocephalus (including
normal-pressure hydrocephalus)
Tumor
Progressive multifocal
leukoencephalopathy
Multiple sclerosis
Abscess
Viral cerebellitis (in
children)
Nutritional deficiency
(vitamin B12, thiamine)
Paraneoplastic syndromes
Drug toxicity (ethanol,
lithium, phenytoin, barbiturates, carbamazepine,
valproic acid, mercury,
toluene)
Essential Tremor
Familial form is autosomal dominant
May involve arms, head, or voice
Action tremor without other neurologic impairment
Suppressed temporarily by ethanol
Physiologic Tremor
Usually a fine postural tremor
Often improves with -blockade
2
Chorea
Wilson Disease
Can present as chorea or various other movement disorders
277
Mental status change, psychiatric disturbance, hepatitis, cirrhosis, dysarthria may accompany or precede the movement
disorder
If young patient, a high level of suspicion is required.
Huntington Disease
Autosomal dominant inheritance
Psychiatric disturbance may occur before chorea.
Dystonia
Acute Dystonic Reaction
Produces variable abnormal and uncomfortable postures,
sometimes including oculogyric crisis
Typically follows new administration of a dopamine
blocker
Most common in young adults
Ataxia
Normal-Pressure Hydrocephalus
Classic triad: dementia, gait ataxia, urinary incontinence
Head imaging shows dilated ventricles, but CSF pressure is
normal.
May improve after lumbar puncture
Multiple Sclerosis
History may suggest previous (sometimes transient) neurologic impairment.
Involvement of two separate neural systems of central nervous system at two separate times is required for diagnosis.
MRI often shows white matter lesions but findings are nonspecific
TEST ORDERING
CT of Head
Useful in acute situations such as ischemic or hemorrhagic
stroke
Can define mass lesions and hydrocephalus
Usually available on urgent or emergent basis
Currently the first choice for initial stroke imaging (because
of its speed and sensitivity for hemorrhage)
Low yield for most movement disorders
278
I SIGNS & SYMPTOMS

MRI of Head
More useful than CT for evaluating nonhemorrhagic
ischemia, demyelinating disease, disease of posterior fossa
(brainstem and cerebellum)
Emergent availability of MRI is less than for CT
Requires prolonged patient immobolization
Drug Levels
Should be determined as applicable
Serum Creatinine and BUN

An increase points to uremia as the cause.
CSF
Should be examined if meningitis or encephalitis is suspected (usually after CT to rule out mass effect)
EEG
Useful when epileptic movements are a consideration
Thyroid-Stimulating Hormone and Glucose

Check levels when evaluating enhanced physiologic tremor.
Wilson Screen
All children and young adults with hyperkinetic movement
disorders should have screening test for Wilson disease.
Initial testsliver enzymes, serum ceruloplasmin, 24-hour
urine for copper, ophthalmologic exam for Kayser-Fleischer
rings
MANAGEMENT
Parkinson Disease
Often managed by neurologists
Many dopamine agonists and anticholinergic agents are available for treatment.
Excessive dopamine may cause dystonia, chorea, hallucinations, or sleep disturbance.
Treatment of psychosis in Parkinson patients should not include
279
traditional neuroleptics; low-dose atypical neuroleptics such

as quetiapine (Seroquel) are less likely to worsen rigidity or
tremor.
Drug-Induced Parkinsonism
Withdraw the offending drug.
If withdrawal is not possible, addition of anticholinergic
(benztropine, trihexyphenidyl) may reduce symptoms.
Anticholinergics may cause cardiac dysfunction, urinary
retention, and confusion, especially in elderly patients.
Acute Dystonic Reactions

Withdraw the offending drug.
IV diphenhydramine or benztropine is often promptly
effective.
Essential Tremor
-Blocker therapy (propranolol), be careful if patient has
respiratory disease, congestive heart failure, or hypotension
Second-line agentprimidone
Restless Legs Syndrome

Treatmentnighttime dopamine agonists (levodopa/carbidopa [Sinemet], pramipexole [Mirapex], ropinirole
[Requip]), clonazepam, or opiates (propoxyphene, codeine)
Wilson Disease
If diagnosis is confirmed, treatment involves copper chelation, usually with penicillamine, which has many side effects.
Tourette Syndrome
Clonidine is sometimes used but is seldom effective.
In severe cases, treatment with small oral doses of haloperidol
or pimozide is often helpful.
Pimozide may prolong QT interval dangerously.
Tardive dyskinesia is serious potential side effect of neuroleptic use.
280
II LABORATORY DIAGNOSIS
ARTERIAL BLOOD GASES
Grace K. Dy, M.D.
Kaiser G. Lim, M.D.
BLOOD GAS VALUES

Arterial pH
Arterial oxygen pressure (PaO )
2
Arterial carbon dioxide pressure (PaCO )
2
Arterial oxygen saturation (SaO )
2
Mixed venous oxygen pressure (PvO )
2
Mixed venous oxygen saturation (SvO )
2
7.35-7.45
75-100 mm Hg
35-45 mm Hg
95%-100%
38-42 mm Hg
70%-75%
INDICATIONS
To assess adequacy of oxygenation for diagnostic and therapeutic purposes
To determine adequacy of ventilation or carbon dioxide
clearance
To assess acid-base status
OXYGENATION VARIABLES
Arterial oxygen saturation (SaO2)
Arterial oxygen content (CaO )
2
Arterial oxygen pressure (PaO )
2
Arterial carbon dioxide pressure (PaCO )
2
Alveolar-arterial oxygen gradient [P(A-a)O ]
2
Arterial-alveolar oxygen ratio (PaO /PAO )
2
2
PaO /FIO ratio (FIO = fraction of inspired oxygen)
2
2
2
Arterial Oxygen Saturation (SaO2)

Oxygen saturation of hemoglobin varies with PaO2.
With the sigmoid characteristic of oxygen saturation curve,
Special abbreviations used in this chapter: ABG, arterial blood gas; V/Q, ventilation-perfusion.
281
the plateau phase is reached at a partial pressure of oxygen

(pO2) of 60 mm Hg (SaO2 of 90%).
Practical and most important measurement in titrating oxygen
therapy: component in determining oxygen content
Inability to maintain SaO2 >90% is considered an indication
for oxygen supplementation and, in the acute setting, mechanical ventilation.
Except in methemoglobinemia, sulfhemoglobinemia, certain
hemoglobinopathies, and carbon monoxide poisoning,
measured oxygen saturation mirrors measured PaO2.
Hemoglobin levels do not affect SaO2.
Anemia causes dyspnea by decreased oxygen carrying
capacity and delivery to peripheral tissues.
SaO2 can be measured with carbon monoxide oximeters and
modern arterial blood gas (ABG) machines
Arterial Oxygen Content (CaO2)

Minimal information needed to assess adequacy of oxygenation and to guide oxygen therapy
A vital component in determining what we can control for tissue perfusion
Oxygen delivery depends on both CaO and cardiac output
2
CaO = 1.39 SaO hemoglobin + 0.0031 (PaO )
2
2
2
Normal value, 18-21 mL O /dL
2
Hemoglobin is equally important because most of the oxygen is transported bound to hemoglobin.
CaO does not measure peripheral tissue oxygenation, which
2
is the ultimate goal. It is not sufficient for assessing patients
with critical illnesses, e.g., shock, sepsis, or compromised cardiac function.
Arterial Oxygen Pressure (PaO2)

Reflects alveolar oxygen pressure (PAO2) and the alveolar
air-pulmonary capillary interface
Not affected by hemoglobin levels
PaO does not have a linear relation with SaO .
2
2
Decreases by 1.2 mm Hg for every 1 mm Hg increase in
PaCO2
Reduced pulmonary diffusing capacity does not always result
in clinically important resting hypoxemia. However, it can
contribute to hypoxemia during exercise.
282
Decreases
. . with age as a result of shifts in ventilation-perfusion (V/Q) ratios in the aging lung
Simple way to estimate age-dependent norm at room air:
PaO2 = 100 (age/3)
Alveolar Oxygen (PAO2) Equation

PAO = FIO (PB 47) (PaCO 1.2) (for FIO <0.60)
2
2
2
2
PAO = FIO (PB 47) PaCO (for FIO 0.60)
2
2
2
2
where PB is barometric pressure (760 mm Hg at sea level)
and water vapor pressure is 47 mm Hg when fully saturated
at 37C
Significance
Low barometric pressure results in a low PAO if FIO remains
2
2
constant.
Low FIO (e.g., mouth-to-mouth ventilation) results in a low
2
PAO2.
Increasing PaCO decreases PAO (and vice versa).
2
2
Alveolar-Arterial O2 Gradient [P(A-a)O2]
P(A-a)O2 = PAO2 PaO2
Used to evaluate adequacy of oxygen transfer
Varies with age, increasing after age 40
Predicted A-a O gradient at room air with adjustment for
2
age:
Age/4 + 4
P(A-a)O determination is most useful when FIO is 0.21.
2
2
Thus, normal P( A -a) O
2 value is both age- and F IO 2 dependent.
For FIO2 of 21%, 5-25 mm Hg
For FIO2 of 100%, <150 mm Hg
A large A-a gradient with patient receiving 100% supplemental oxygen reflects either a physiologic or anatomical
shunt (e.g., left-to-right heart shunt)
A normal A-a gradient (5-25 mm Hg on room air) indicates
that hypoxemia is due to hypoventilation or low FIO2.
However, prolonged hypoventilation can lead to areas of
atelectasis and thus an increase in the A-a gradient.
283
Arterial-Alveolar O2 Ratio
An alternative to P(A-a)O for evaluating adequacy of oxy2
gen transfer
With increasing F IO , Pa O /P AO varies much less than
2
2
2
P(A-a)O2.
This is a more stable variable, remaining fairly constant with
increasing FIO2 as long as the underlying lung condition
does not vary; hence, it is useful in the short term (hourly) and
in assessment of oxygenation.
Normal PaO /PAO ranges from 0.74 in elderly people to
2
2
about 0.9 in young subjects (usual range, 0.77-0.82)
Most reliable when FIO is <0.55
2
PaO2/FIO2 Ratio
Another alternative to P(A-a)O for evaluating adequacy of
2
oxygen transfer
Obviates need to calculate PAO
2
Is used as part of the diagnostic criteria for acute lung injury
(<300) and acute respiratory distress syndrome (<200 regardless of positive end-expiratory pressure level)
Most reliably assessed at an FIO of 0.5
2
Limitationdoes not account for PaCO , but this is not impor2
tant at high FIO2.
Normal PaO /FIO by age
2
2
60 years: 400-500
>60 years: 400 [5 (age 60)]
VENTILATORY VARIABLE
Arterial Pressure of Carbon Dioxide (PaCO2)
Necessary for evaluating oxygenation (alveolar oxygen
equation)
Reflects adequacy of alveolar ventilation relative to carbon
dioxide production
An important component of acid-base balance (HendersonHasselbalch equation)
Never diffusion-limited
Increased physiologic dead space, resulting from V/Q mismatch or severe restrictive disease, is a more common cause
of increased PaCO2 than hypoventilation.
284
In a Nutshell
In the acute setting, if the saturation is 90% on room air,
order an ABG.
Confirm hypoxia and rule out possible causes (Fig. 1).
First, rule out acute hypercapnia (i.e., respiratory failure)
Second, observe response to supplemental oxygen (V/Q
mismatch vs. shunt)
If hypercapnia is not a problem, oxygen titration can be
done while monitoring saturation.
If hypercapnia is a problem (e.g., COPD), monitor oxygen
supplementation with another ABG 10-15 minutes after
change in therapy.
285
SaO2
Decreased
PaO2
Normal
CO
MetHb
Decreased
PaCO2
P(A-a)O2 gradient
Normal
High
Hypoventilation
Central
Neuromuscular
Increased
Normal/low
Improves
with O2
High altitude
(low FIO2)
Yes
V/Q mismatch
Parenchymal
lung disease
Obstructive
lung disease
Pulmonary
vascular
disease
No
Shunt
Atelectasis
Alveolar
flooding
(ARDS,
pneumonia)
Pulmonary
AVM
Intracardiac
shunt
Fig. 1. Algorithm for work-up if oxygen saturation is 90% on room

air. ARDS, acute respiratory distress syndrome; AVM, arteriovenous
malformation; CO, carbon monoxide toxicity; FIO2, fraction of inspired
oxygen; MetHb, methemoglobinemia; SaO2, arterial oxygen saturation; V/Q, ventilation/perfusion.
286
CARDIAC BIOMARKERS
Dariush S. Takhtehchian, M.D.
PATHOPHYSIOLOGY OF INCREASED CARDIAC
ENZYME LEVELS
Acute coronary occlusion interrupts blood flow to the
myocardium and causes necrosis of myocytes, which leads
to loss of cell membrane integrity and release of cellular
macromolecules. Myocyte necrosis results in the appearance
of biomarkers in the plasma.
CLINICAL IMPORTANCE
Allows for early diagnosis of acute myocardial infarction
(MI)
Cardiac enzymes differentiate between
NonST-segment elevation MIincreased serum markers
Unstable anginano serum markers released
Cardiac enzymes provide risk stratification and prognostic
information in acute coronary syndromes (e.g., high early
levels predict more complications).
TYPES OF CARDIAC BIOMARKERS

Troponin (Table 1)
Cardiac-specific subtypes (I, T) are measured by current
assays.
Accuracy depends partly on assay coefficient of variation
(<10% ideal).
Most accurate and specific measure of myocyte necrosis
Appears in plasma 2-4 hours after onset of necrosis
May remain elevated for days
Very sensitive bioassay; may be elevated in conditions
other than acute MI, such as congestive heart failure, pul-
Special abbreviation used in this chapter: MI, myocardial infarction.

287
Table 1. Differential Diagnosis of Elevated Cardiac

Troponins
Acute myocardial infarction; there is a rapid rise and fall in levels
in patients with cardiac ischemia
Congestive heart failure or circulatory volume overload
Pulmonary embolism
Hypertensive crisis
Infiltrative cardiomyopathies
Myocarditis or myopericarditis
Cardiac injury secondary to chemotherapy or other toxins
Hypotensive spell with watershed territory-associated myocyte
necrosis
Anemia with watershed territory-associated myocyte necrosis
Septic or hypovolemic shock with associated myocyte necrosis
Valvular heart disease-associated myocyte necrosis from pressure
and/or volume overload
Pressor agent-associated myocyte necrosis
Apical ballooning syndrome
monary embolism, hypertensive crisis, myocarditis,

myopericarditis, traumatic injury, and drug toxicity
Troponin I and troponin T are both useful and equal in
diagnostic utility.
Not elevated in renal failure per se, but is a high-risk marker when elevated in patients with renal failure
CK, CK-MB
Muscle enzyme expressed in skeletal, cardiac, and smooth
muscle types
CK-MB is highly expressed in cardiac myocytes.
Appears in plasma 4-6 hours after onset of myocyte
necrosis
Equal sensitivity to cardiac troponins but less specific
Can be elevated from skeletal muscle injury and after
operations on organs that express CK-MB
Myoglobin
A heme protein found in many tissues
Elevated very early after onset of myocyte necrosis, appearing as early as 90 minutes after symptom onset in one study
Not specific for the heart and may be elevated for other
288
reasons
Release and metabolism may follow an undulating pattern
and so may be at a nadir when measured, masking
diagnosis of acute MI.
Should be used in combination with troponin for diagnosis
of acute MI
C-reactive protein
Inflammatory marker protein, elevated in many conditions
Excellent marker for future cardiovascular risk when
elevated (3 mg/L) in patients with no underlying inflammatory or malignant conditions
Treatment optionsaspirin, statin, lipid-lowering therapy, weight loss, regular exercise, more aggressive control
of diabetes
B-type natriuretic peptide
Released from cardiac myocytes (ventricular >> atrial)
secondary to increased filling pressures and in congestive
heart failure and restrictive cardiomyopathies
Very sensitive diagnostic marker for acute heart failure
Confers prognostic information in acute coronary
syndromes
289
CHEST X-RAY
Sean M. Caples, D.O.
Edward C. Rosenow III, M.D.
BASIC APPROACH
The importance of a thorough review of a chest X-rayUp to
19% of lung cancers of any size and 90% of early (<1 cm)
peripheral solitary lung cancers are missed on chest X-rays.
Primary care providers should develop a comfort level for
viewing chest X-rays of all their patients.
The key to interpreting a chest X-ray is to read hundreds of
normal ones. With experience, you will recognize abnormalities more readily, even without knowing what the abnormality is.
Read the chest X-ray before you read the radiologists report.
It has been estimated that radiologists miss 10%-15% of
abnormalities on chest X-rays.
Describe what you see without necessarily making a diagnosis
immediately.
Do not concentrate on a single abnormality; there may be
others.
Make every attempt to compare a new film with old films.
Begin by looking at the X-ray from 6-8 feet away.
Never accept the reading of a chest X-ray as normal.
Assess the technical adequacy of the study.
Be sure the entire thorax is seen.
Check the symmetry of the clavicle to assess patient
rotation.
With proper X-ray penetration, the lower thoracic vertebrae behind the heart should be faintly visible.
A bright or hot light may be helpful for faint or underpenetrated exams.
Develop your own systematic review of chest X-rays and be
consistent. Use whatever system you are comfortable with,
291
but be sure to include

Chest wall
Lung parenchyma and large airways
Mediastinum
Chest Wall
Look for pleural thickening or calcification.
Costophrenic angles are normally sharp (200-400 mL of
pleural fluid is required to blunt the angles).
Diaphragm
Right hemidiaphragm is normally higher than the left
Subpulmonic effusion may resemble an elevated
diaphragm without blunting of the costophrenic angles
(decubitus film may be required to demonstrate effusion).
Bony abnormalities (metastases), rib notching (coarctation),
extrathoracic soft tissues (neck, tracheal masses), shoulder
joints
Lung Parenchyma and Airways

Comparing left and right symmetry is most helpful.
About 15% of the lung parenchyma is hidden by cardiovascular
structures and the left diaphragm on front view X-rays; lateral films are helpful in identifying lesions hidden in this area.
Look carefully behind the heart, diaphragm, and mediastinal
structures.
Carefully scan the apices under the clavicles and first rib.
Try not to overinterpret interstitial markings, which may be
accentuated by a submaximal inspiration. (If inspiration
was adequate, it should be possible to count 10 ribs above the
right costophrenic sulcus.)
Normal lung markings (which are predominantly vascular
structures) should disappear within about 1 cm of the pleural surface; visible markings extending to the pleura suggests an abnormality (e.g., Kerley B lines); compare the new
film with old films.
Mediastinum
Familiarize yourself with the normal silhouette.
The left hilus is up to 3 cm superior to the right hilus in 95%
of normal persons. An elevated right hilus may suggest volume loss on that side.
292
Know the mediastinal compartments and common abnormalities of each.

Superiorthyroid, aortic arch aneurysm
Anteriorneoplasms of various origins
Middlelymph nodes, heart, great vessels, esophagus
Posteriorneurogenic tumors
Anteroposterior (portable) films magnify heart size and mediastinum
CT usually is needed to further characterize mediastinal
abnormalities.
SOME PATTERNS OF ABNORMALITIES

Airspace-Filling Disorders
These typically have ill-defined borders and may be referred
to as consolidation.
Focal (involving segment or lobe)
Pneumonia (bacterial, viral)
Pulmonary embolus with infarction
Neoplasm (bronchoalveolar cell carcinoma, lymphoma)
Contusion
Diffuse or patchy/multifocal
Pulmonary edema
Infection (TB, Pneumocystis jiroveci [formerly carinii]
pneumonia, other)
Hemorrhage
Neoplasm (lymphoma)
Two Typical Radiographic Findings
Air Bronchogram
Visible air-filled bronchus is surrounded by fluid-filled lung.
This occurs when fluid accumulates in the alveoli but not in
the conducting airways.
Silhouette Sign
The loss of the normal air-fluid interface caused by accumulation of fluid within the air spaces. For example, the
border of the right side of the heart normally is visualized in
sharp contrast against the air-filled right middle lobe. With
293
pneumonia in this lobe, the border of the right side of the

heart is lost or silhouetted out.
Interstitial Patterns
The accumulation of fluid or cells in the interstitial tissue
May coexist with air-space filling radiographically
Fine Reticular Pattern

May be acute (Kerley B lines of cardiogenic pulmonary
edema, viral pneumonia)
May be chronic (interstitial lung disease/idiopathic pulmonary fibrosis or hypersensitivity pneumonitis)
Nodular Pattern
Miliary TB, fungal disease, sarcoidosis, metastases, alveolar cell carcinoma
Coarse Reticular Pattern

Honeycombing of advanced idiopathic pulmonary fibrosis
May also be seen with pulmonary edema superimposed on
emphysema
Nodule
A well-defined opacity <3 cm in diameter
Is completely surrounded by aerated lung space in the absence
of an effusion
Solitary Pulmonary Nodule

Neoplastic (malignant 30% vs. benign 70%) or infectious
granuloma
Multiple Nodules
Metastases, inflammatory (rheumatoid, Wegener granulomatosis), septic emboli
Mass
Similar to a nodule but is >3 cm in diameter
More than 90% are malignant
Increased Lung Radiolucency (Decreased Opacity)

Air trapping in acute, severe asthma (diffuse) or foreign body
294
aspiration (regional)
Emphysema with or without bullae
Pulmonary embolism with regional oligemia
SELECTED CLINICAL APPLICATIONS

Pneumothorax
Spontaneous or secondary (COPD, ruptured bullae, trauma,
Pneumocystis jiroveci pneumonia)
Most often identified as a white line (visceral pleura) abutted
by a paucity of lung markings peripheral to it
The collapsed lung is not always denser than the contralateral lung.
Radiodensity depends on vascular markings, and the pneumothorax causes regional oligemia.
Importance of patient position
Upright (preferred)small collections of air usually seen
in the apex (often lateral apex)
Recumbentrequires larger volumes of air to appreciate
May see subpulmonic air, a collection along the anterolateral mediastinum or
Deep sulcus signa deep and wide costophrenic sulcus
(between the lateral chest wall and diaphragm)
If the patient cannot sit upright, obtain a lateral decubitus
film; air will rise to the upper edge of the lateral chest
wall.
Expiratory films may be helpful if the diagnosis is in question, because lung tissue becomes denser and the visceral
pleura may be identified more readily. However, the study
of first choice is plain inspiratory films.
Pitfalls
Skin folds or bed sheets, particularly with portable films
These lines often extend out of the thorax or may have
lung markings peripheral to them.
Large bullae may mimic a pneumothorax.
Tension pneumothorax is a clinical diagnosis (hypotension,
unilaterally absent breath sounds, and tracheal deviation)
and decompression must be performed without waiting for
the chest X-ray. It is possible for a stable, nonventilated
295
patient to demonstrate radiographic signs of a tension pneumothorax, which include ipsilateral hemidiaphragmatic
depression and shift of the trachea and mediastinum away
from the collapsed lung.
Any size pneumothorax is important in a mechanically ventilated patient where there is always a risk of a tension pneumothorax.
Cardiovascular Findings
Normal Contours of the Mediastinum
Right paratracheal stripe (air-lung interface) is normally up
to 5 mm in diameter.
Widening here may be due to lymphadenopathy or fat.
The inferior portion is continuous with the azygous vein.
Aorticopulmonary window
The space below the aortic arch and above the left pulmonary artery
Obliteration of this space suggests adenopathy or tumor.
Heart Size and Chambers
Loss of the normal heart contour may represent chamber
enlargement or pericardial effusion.
Horizontal width of the heart normally should be no more
than half the width of the thorax (cardiothoracic ratio).
Hila
The normal branching, vascular appearance is lost with
lymphadenopathy or tumor.
Pulmonary arterial hypertension is suggested by engorged
pulmonary arteries that rapidly taper (pruned tree).
Pulmonary venous hypertension causes prominence of
the superior veins in the upper zones of the hila.
Congestive Heart Failure

Generalized or focal chamber enlargement
Pulmonary edema
Cephalization early (increased upper zone markings)
Later, you see evidence of interstitial edemaKerley B
lines (thickening of interlobular septae), peribronchial
cuffing (thickening), pleural effusions, prominent superior pulmonary veins.
296
Alveolar filling, often with a perihilar or bat-wing distribution
Note: Kerley B lines are also seen in lymphangitic carcinoma and, less often, in interstitial disease.
Thoracic Aortic Aneurysm or Dissection

May affect any part of the thoracic aorta
Associated with poorly controlled hypertension and Marfan
syndrome
Dissection usually presents with acute, typical symptoms
but may be found incidentally on chest X-ray weeks after
the event.
The film should be compared with previous ones to assess for
enlargement.
Up to 20% of chest X-rays that show dissection are interpreted as normal.
Some radiographic features
Widening, blurring, or irregularity of the aortic silhouette
Calcium signMore than a 6-mm separation of the calcified intima from the outer aortic wall of the ascending or
descending aorta may suggest dissection.
Displacement of other thoracic structures
Rightward shift of trachea or esophagus
Inferior displacement of left mainstem bronchus
Widened mediastinum or pleural effusion (usually leftsided) may suggest hemorrhage or leakage.
Further imaging is mandatory, such as CT, transesophageal
echocardiography, or MRI.
Coarctation of the Aorta

Congenital band-like narrowing of aorta that most often
occurs just distal to the origin of the left subclavian artery,
although site of origin may vary
Milder degrees of narrowing may present in adulthood with
hypertension of the upper extremities.
Classic chest X-ray findings in adults
Rib notchingThis results from prominent tortuous intercostal collateral vessels along the posterior inferior portion
297
of ribs 3 through 8, which bypass the aortic narrowing to

supply the descending aorta.
Irregular contour of the upper descending aorta
Prestenotic and poststenotic dilatation may form the 3
sign just superior to the left main pulmonary artery
Associated with bicuspid aortic valve and intracerebral
aneurysms.
Pulmonary Embolism
Chest X-ray has very low sensitivity and specificity.
Some radiographic features
Normal chest X-ray in ~1/3 of patients
Atelectasis, hemidiaphragm elevation
Westermark signlocalized parenchymal oligemia
Hampton humppleural-based, wedge-shaped opacity
suggestive of pulmonary infarction (rare)
Pleural effusion
Enlarged pulmonary artery or arteries
Consider CT angiography, ventilation-perfusion scan, deep
venous duplex ultrasonography
Volume Loss With or Without Atelectasis

Causes
Endobronchial obstruction
May be due to foreign body or mucus plugging
Bronchogenic carcinoma must be ruled out.
Compressive atelectasisfrom effusions or pleural-based mass
Hypoventilation can cause discoid (linear) atelectasis (seen
in bedridden or splinting patients)
Radiographic Findings
About 25% of cases lack chest X-ray findings.
Findings may include
Displacement of the interlobar septa bounding the affected lobeThis is the most direct and reliable sign.
Hemidiaphragmatic elevation
Mediastinal shift on the obstructed side
Narrowing of rib margins
Hyperinflation or oligemic changes of the remaining
lobe(s) or contralateral lung
Reverse S sign with collapse of the right upper lobe
298
Pleural Effusion
Layering of effusion confirmed by lateral decubitus film,
also confirms a subpulmonic effusion that may not blunt the
costophrenic angle
If in doubt, perform thoracentesis with ultrasound guidance.
During or after a thoracentesis, if the patient develops cough,
shortness of breath, or chest pain or becomes hypotensive,
obtain a chest X-ray to rule out pneumothorax.
CHEST X-RAY AND DIFFERENTIAL DIAGNOSES
Common differential diagnoses based on the chest X-ray
pattern are listed in Table 1.
ATLAS OF CHEST X-RAYS

Figures 1-10.
299
Table 1. Common Differential Diagnoses Based on

Chest X-ray Pattern
Consolidation in a nonsegmental distribution with air bronchograms
Infectionbacterial (most commonly pneumococcus), fungal
Neoplasialymphoma, bronchoalveolar cell carcinoma
Inflammatorypulmonary infiltrates with eosinophilia
syndrome, bronchiolitis obliterans-organizing pneumonia
Traumacontusion, irradiation pneumonitis
Segmental consolidation with mild atelectasis (usually without air
bronchogram)
Infectionbronchopneumonia (bacterial [including
mycoplasma], fungal, viral)
Inflammatoryallergic bronchopulmonary aspergillosis,
Neoplasiabenign, primary, or metastatic malignancy
Otheraspiration, postoperative atelectasis, pulmonary
infarction
Cystic and cavitary disease
Congenitalbronchopulmonary sequestration (almost always
in lower lobes)
Infectionbacterial (rule out TB), fungal, parasitic, septic
emboli
InflammatoryWegener granulomatosis, rheumatoid
nodules, sarcoidosis
Neoplasiasquamous cell carcinoma (more commonly),
metastatic disease
Inhalationalpneumoconiosis (silicosis)
Solitary or multiple pulmonary nodules
Congenitalbronchial cyst, arteriovenous malformation
InfectionTB, fungal, parasitic (if multiple, think of septic
emboli)
InflammatoryWegener granulomatosis, rheumatoid nodule
Neoplasiacarcinoid, hamartoma, primary & metastatic
carcinoma
Otheramyloidosis, hematoma
Diffuse (bilateral) alveolar infiltrates (airspace disease)
Infectionviral, airway spread of TB, histoplasmosis
Inflammatoryalveolar hemorrhage syndrome, vasculitis
Neoplasiametastatic disease, bronchoalveolar cell
carcinoma
Pulmonary edemacardiogenic, noncardiogenic
Embolicfat or amniotic fluid
Drug or inhalation injury
Alveolar proteinosis
300
Table 1 (continued)
Diffuse disease with predominant reticular or reticulonodular
pattern
Infectionrule out miliary TB
Inflammatoryconnective tissue diseases
Neoplasialymphangitic carcinomatosis
Inhalationalsilicosis
Drug effects
Idiopathic pulmonary fibrosis, histiocytosis X,
lymphangioleiomyomatosis
Isolated pleural effusion (without other abnormalities on chest X-ray)
InfectionTB, subphrenic abscess
Inflammatoryconnective tissue disease
Neoplasialymphoma, metastatic disease
Embolicpulmonary embolism
Trauma
Metabolicrenal, thyroid, liver disease
Mediastinal abnormalities by compartment
Superior (above aortic arch)
Thyroid (>90%)
Neurogenic neoplasia
Vascular structures (aneurysms)
Anterior (bordered by sternum anteriorly and heart, great
vessels posteriorly)
Lymphoma, most commonly Hodgkin disease
(particularly if <30 years old)
Thymoma (most common if >30 years old)
Germ cell tumors
Castleman disease (angiofollicular giant lymph node
hyperplasia)
Middle (contains heart & great vessels, large airways,
esophagus, vagus & phrenic nerves)
Lymph node enlargement (lymphoma, metastases,
granulomatous disease)
Fibrosing mediastinitis (most often due to histoplasmosis)
Bronchogenic, enterogenous, and pleuropericardial cysts
Esophageal lesions
Mediastinal vessel enlargement (coarctation, aneurysm)
Posterior (between the anterior aspect of vertebral column
& posterior chest wall)
Neurogenic tumorsmay arise from peripheral nerves
(neurofibromas or schwannomas), sympathetic ganglia
(ganglioneuromas), or paraganglion cells (pheochromocytomas)
301
Fig. 1. Normal posteroanterior and lateral chest X-ray of a young man.
Fig. 2. A 50-year-old woman had right mastectomy for breast cancer.

One year later, the follow-up film showed a right paratracheal fullness, which was found to be metastatic adenopathy.
302
Fig. 3. Left, Diffuse interstitial infiltrates and pulmonary venous

hypertension from congestive heart failure. Right, 12 hours later following diuresis. Note cardiac enlargement.
Fig. 4. Left, Baseline chest X-ray of middle-aged man. Right, Portable

film after acute pulmonary embolism. Note enlarged right pulmonary
artery, right hemidiaphragm elevation, and right basilar oligemia
(Westermark sign).
303
Fig. 5. Coarctation of aorta. Note notching of inferior surface of ribs

and irregular contour of upper aorta (the 3 sign).
Fig. 6. Posteroanterior and lateral views of collapsed left lower lobe.

Note displaced hilum, volume loss, and relative parenchymal lucency
(compensatory hyperinflation) on the left. Also note nodular density
of left midlung.
304
Fig. 7. Posteroanterior and lateral films showing left upper lobe collapse resulting from a broncholith (calcified hilar node that has eroded through bronchus). Lobar boundary is easily seen on lateral film,
but also note the elevated hemidiaphragm and relative ground-glass
density of upper lung field on the left in the posteroanterior film.
Fig. 8. Reverse S sign is indicative of right upper lobe collapse

caused by an obstructing airway mass. The lower half of the S is a
bronchogenic carcinoma.
305
Fig. 9. Lymphangitic metastases in a 25-year-old woman with breast

cancer. Diffuse reticulonodular infiltrates with Kerley B lines are seen
in the right base. Also note the right paratracheal and hilar adenopathy
and small bilateral pleural effusions.
Fig. 10. Right paratracheal and bilateral hilar adenopathy in a young

woman with stage I sarcoidosis who presented with arthralgias and
erythema nodosum. Histoplasmosis may present in a similar fashion
and must be considered in the differential diagnosis.
306
COAGULATION PANEL
Karin F. Giordano, M.D.
Rajiv K. Pruthi, M.D.
DECISION TO PERFORM HEMOSTATIC TESTING

The key to deciding to perform hemostatic testing and choosing the appropriate coagulation tests lies within the patients
history.
The first step is to determine if the patients problem is hemostasis (i.e., excessive bleeding) or thrombosis (i.e., hypercoagulability).
After this has been determined, testing can be appropriately ordered and interpreted.
EVALUATION OF BLEEDING DISORDERS
Bleeding History
The history continues to be important to guide testing.
The aims of obtaining a detailed hemostatic history are to
determine if there is a bleeding disorder and to differentiate
a congenital from an acquired bleeding disorder.
Questions to ask
Is the bleeding problem lifelong or new? Bleeding during
previous surgical procedures is a useful historical factor
(remember to ask about wisdom tooth extraction).
Is there a family history of bleeding? It may be useful to
ask for presence of specific bleeding disorders (e.g., hemophilia, von Willebrand disease).
Is the patient taking drugs that predispose to bleeding?
Consider heparin, warfarin, NSAIDs, and aspirin as potential causes.
Ask about the nature of bleeding. Some clinical clues
include
Special abbreviations used in this chapter: DRVVT, dilute Russell viper venom
time; RT, reptilase time; TT, thrombin time.
307
Mucous membrane bleeding, petechiaeplatelet dysfunction, von Willebrand disease

Hemarthrosishemophilia
Soft tissue hematomasdefect in coagulation cascade
(e.g., hemophilia or other factor deficiency)
Immediate bleeding at time of surgerydefect in primary hemostasis
Bleeding after initial adequate hemostasisfactor
deficiency
Marked delay in bleedingfactor XIII deficiency
Screening Tests
The history may allow the physician to focus on particular
testing. For example, a history of petechiae or spontaneous
bruising may lead the clinician to focus on platelet studies,
whereas a family history of hemophilia would lead to detailed
testing for factor deficiencies.
For patients with a history suggestive of a bleeding disorder, the following screening tests are recommended:
Tests of Coagulation
The extrinsic, intrinsic, and common coagulation pathways
are shown in Figure 1.
The differential diagnosis for abnormal screening test results
is listed in Table 1.
aPTT
Measures the integrity of the intrinsic and final common
pathway, i.e., prekallikrein, high-molecular-weight
kininogen, and factors I (fibrinogen), II, V, VIII, IX, X,
XI, XII
Most sensitive to deficiencies of factors higher up in the
intrinsic pathway
Depending on the sensitivity of the aPTT reagents,
aPTT may be normal or only slightly prolonged in mild
hemophilia (factor VIII or IX deficiency)
PT
Measures integrity of extrinsic and final common pathway, i.e., factors I (fibrinogen), II, V, VII, X
PT is not prolonged by heparin, because of a heparin neutralizer in the reagent.
308
Extrinsic pathway
Intrinsic pathway
Prekallikrein
HMWK
Tissue factor
aPTT
PT
XIIa
XII
VIIa
VII
Fig. 1. The coagulation

cascade. DRVVT, dilute
Russell viper venom time;
HMWK, high-molecularweight kininogen.
XIa
IX
IXa
VIIIa
DRVVT
Xa
Va
Prothrombin (II)
Thrombin (IIa)
Fibrinogen
Fibrin
XIIIa
XIII
IIa
309
Cross-linked fibrin clot
XI
Table 1. Differential Diagnosis for Prolonged Screening

Test Result
Screening
test
aPTT
PT
DRVVT
TT
RT
Drugs
Inhibitors
Factor deficiency
Heparin, Factor VIII inhibiXII, XI, IX, VIII

warfarin, tors are relatively
X, V, fibrinogen,
DTIs*
common
liver disease, vitaOther factor inhibimin K deficiency,
tors are rare
DIC
Lupus anticoagulant
Warfarin, Factor V inhibitors VII, X, V, fibrinogen, liver disease,
DTIs*
DIC, vitamin K
deficiency
Heparin, Lupus anticoagulant X, V, fibrinogen,
warfarin, Factor V inhibitors
vitamin K deficiDTIs*
ency, DIC
Heparin, Bovine thrombin
Dysfibrinogenemia,
inhibitor
hypofibrinogenemia,
DTIs*
afibrinogenemia,
DIC
Not hep- Not heparin
Dysfibrinogenemia,
arin
hypofibrinogenemia,
afibrinogenemia,
DIC
DIC, disseminated intravascular coagulation; DRVVT, dilute Russell viper

venom time; DTI, direct thrombin inhibitor; RT, reptilase time; TT, thrombin
time.
*Examples, lepirudan, argatroban, bivalirudin.
Generally, abnormalities of PT or aPTT reflect either coagulation factor deficiency or presence of an inhibitor to one or
more of the coagulation factors listed. The differentiation is
made by performing mixing studies (see below).
INR
Standardized formula to reflect changes in PT secondary
to oral anticoagulation
INR = (patient PT/mean normal PT)ISI
ISI (international sensitivity index) represents sensitivity
of thromboplastin to decrease of vitamin K-dependent
factors (II, VII, IX, X). This information is supplied by the
manufacturer of the PT reagents.
310
INR is meant only for monitoring oral anticoagulation.
Dilute Russell viper venom time (DRVVT)
Snake venom used to measure common pathway
Directly activates factors V and X
Part of screening for lupus anticoagulant (see below)
Thrombin time (TT)
Measures conversion of fibrinogen to fibrin; bypasses
thrombin
TT is not a measure of thrombin activity.
Reptilase time (RT)
Snake venom that converts fibrinogen to fibrin
Used to determine if prolonged TT is caused by heparin
or a fibrinogen dysfunction or deficiency
If both TT and RT are prolonged, consider either a quantitative or qualitative deficiency of fibrinogen, which
may be acquired or congenital.
If TT is prolonged but RT is normal, think of heparin.
Mixing studies
Used to evaluate prolonged aPTT, PT, or DRVVT.
The patients plasma is mixed with normal plasma in a
1:1 ratio to determine if abnormal aPTT, PT, or DRVVT
corrects.
If it corrects to a normal value, think of factor deficiency, which could be congenital or acquired (e.g.,
liver disease, warfarin).
It if does not correct completely, think of an inhibitor
(specific factor inhibitor, lupus anticoagulant, or heparin).
Factor assays
Factor results are reported as percentage of normal activity.
Factor activity levels are decreased in deficiency or the
presence of inhibitor.
Indications for checking specific factor activity levels
include clinical suspicion of a factor deficiency or abnormal aPTT, PT, or DRVVT.
Abnormal screening test findings and the differential diagnosis for factor deficiencies are listed in Table 2.
Factor inhibitors
Antibodies targeted against a specific factor
311
312
Table 2. Coagulation Factors

Factor
Abnormal tests
Acquired deficiencies
I (fibrinogen)
TT
RT (DRVVT, aPTT,
PT in some cases)
II (prothrombin)
aPTT
PT
DRVVT
aPTT
PT
VII
PT
Dysfibrinogenemia
Hypofibrinogenemia
Liver disease
DIC
Warfarin
Liver disease
Factor inhibitor
Liver disease
Factor inhibitor
DIC
Acute leukemia
Warfarin
Liver disease
Congenital
deficiencies
Increased levels
Clinical hints
Congenital
Afibrinogenemia
(autosomal
dominant)
Autosomal
recessive
Inflammation
(acute phase
reactant)
Chronic hyperfibrinogenemia may predispose

to thrombosis
NA
TT is not a test of
prothrombin activity
Autosomal
recessive
NA
Factor V level is a sensitive

indicator of factor deficiency due to liver failure
Autosomal
recessive
NA
Short half-life of factor VII

causes rapid increase in
PT with warfarin, but
other factors are not yet
decreased enough for true
anticoagulation
Table 2 (continued)
Factor
Abnormal tests
Acquired deficiencies
Congenital
deficiencies
Increased levels
aPTT (may be normal in mild cases)
Factor inhibitor
Hemophilia A
(X-linked)
von Willebrand
disease
Stress
Liver disease
Pregnancy
Estrogen
IX
aPTT (may be normal in mild cases)
Hemophilia B
(X-linked)
NA
aPTT
PT
DRVVT
Warfarin
Liver disease
Factor inhibitor
Warfarin
Liver disease
Factor inhibitor
Amyloidosis
Autosomal
recessive
NA
313
DIC, disseminated intravascular coagulation; DRVVT, dilute Russell viper venom time; TT, thrombin time.
Mild deficiency can

be missedstress/
exercise may transiently increase level
to normal (e.g.,
walking up several
flights of stairs bebefore blood is drawn)
VIII
Clinical hints
Presence of a factor inhibitor is suggested by lack of complete correction of an abnormal aPPT, PT, or DRVVT in
mixing studies.
A decrease in activity level of a specific factor in this setting suggests an inhibitor of that factor.
Most common factor inhibitor is factor VIII inhibitor.
Inhibitors of factors V, IX, X and XI are much less
common.
Factor VIII inhibitors
Alloimmuneinhibiting antibodies that develop in
some hemophilia patients, resulting in poor response
to factor VIII treatments
Autoimmuneusually idiopathic in the elderly; may
be associated with autoimmune disease, malignancy,
lymphoproliferative disease, drugs (penicillin, phenytoin, ampicillin, sulfa).
Bethesda assay
A measure of the amount of factor inhibitor activity,
expressed as Bethesda units (BU).
<1 BU is negative; 1-10 is low.
Platelet Tests
Platelet count
Look for thrombocytopenia.
Confirm low platelet count with a peripheral blood
smear.
If in vitro clumping (pseudothrombocytopenia) is suspected, draw blood in a citrate tube.
Bleeding time
A crude test of the primary hemostatic response (i.e., vasoconstriction, platelet plug formation)
Sensitivity and specificity are low because of variations in
test interpretation.
Platelet aggregation studiesobservation of platelet aggregation in vitro in response to different stimuli
Aggregation with adenosine diphosphate, collagen epinephrineshows abnormalities of fibrinogen binding
(Glanzmann thrombasthenia), arachidonic acid metabolism
(COX inhibition), storage pool disease
Aggregation with ristocetinabnormalities suggest von
Willebrand disease, Bernard-Soulier syndrome
314
Platelet aggregation studies are sensitive to any antiplatelet

agents the patient may be taking. Remember to ask about
over-the-counter analgesics!
EVALUATION OF HYPERCOAGULABLE STATES

Thrombotic History
A thorough history is essential in guiding hypercoagulability testing.
Historical events to consider
Personal or family history of deep venous thrombosis
Oral contraceptives
Recent trauma or surgery
Immobility
Smoking
Malignancy
Fetal loss
Previous arterial events (myocardial infarction, stroke)
A history of arterial or venous thrombosis may guide testing
differently.
Hypercoagulability Testing
Clinical hint: To avoid ambiguity of test results, try to have
blood drawn before starting treatment with heparin and
warfarin.
Acute events (e.g., deep venous thrombosis, stroke) may
affect some test results. Ideally, abnormalities should be
reconfirmed about 4 weeks after the patient stops taking
warfarin.
Details of hypercoagulability testing are outlined in Table
3.
Activated Protein C Resistance/Factor V Leiden

In activated protein C resistance, factor V is resistant to inactivation by activated protein C.
Protein C
Activated by thrombin-thrombomodulin complex to degrade
factors Va and VIII
315
316
Table 3. Hypercoagulability Testing

Frequency
Assay
Thrombosis
type
Thrombosis
risk
Acquired
abnormalities
Activated
protein C
resistance/
factor V
Leiden
Most common
genetic risk factor
for DVT
20% of patients
with idiopathic
venous thrombosis
Suboptimal increase in aPTT

in response to
protein C
Confirm with
PCR for factor
V Leiden
mutation
Venous
Heterozygotes
(3-7 increase)
Homozygotes
(80 increase)
NA
Protein C
deficiency
3% of patients
with idiopathic
venous thrombosis
Protein C antigen & activity
Venous
Warfarin
Vitamin K
deficiency
Liver disease
Protein S
deficiency
2% of patients
with idiopathic
venous thrombosis
Protein S antigen & activity
Venous
Heterozygotes
(7 increase)
Homozygotes
(purpura fulminans)
Heterozygotes
(unknown)
Homozygotes (purpura fulminans)
Warfarin
Vitamin K
deficiency
Liver disease
Clinical hints
Activated protein C
resistance assay is
not reliable if baseline
aPTT is increased
5% of patients with
activated protein C resistance (as measured
by the first-generation
assay) do not have
factor V Leiden
In vitamin K deficiency, protein C &
factor VII should be
decreased proportionally
In vitamin K deficiency,
protein S & factor II
should be decreased
proportionally
Table 3 (continued)
Thrombosis
risk
Acquired
abnormalities Clinical hints
Antithrombin 3%-6% of patients Antithrombin

III deficiwith idiopathic
III antigen &
ency
thromboembolic activity
event
Venous
? Arterial
Heterozygotes
(5 increase)
Homozygotes
(incompatible
with life)
Prothrombin
20210G-A
Venous
? Arterial
Heterozygotes
(2.8 increase)
Homozygotes
Heparin
Warfarin can
Liver disease
cause increased
DIC
level
L-asparaginase
Nephrotic syndrome
Oral contraceptives
NA
6% of patients
with idiopathic
venous thrombosis
Assay
PCR-based
assay
317
Thrombosis
type
Frequency
318
Table 3 (continued)
Frequency
Hyperhomocysteinemia
Assay
10%-25% of patients Homocysteine

with venous
level
thrombosis
Thrombosis
type
Thrombosis
risk
Acquired
abnormalities
Heterozygotes
Venous
Arterial
(unknown)
Atherosclerotic Homozygotes,
disease
(homocystinuria
in childhood)
DIC, disseminated intravascular coagulation; DVT, deep venous thrombosis; PCR, polymerase chain reaction.
Vitamin B12,
B6, or folate
deficiency
Renal failure
Hypothyroidism
Phenytoin
Methotrexate
Clinical hints
Treat with folate,
vitamin B12, B6
Could check
MTHFR gene1
mutation found in
some people with
increased homocysteine
Protein S
Acts as a cofactor with protein C to inactivate factors Va and
VIIIa
Antithrombin III Deficiency
Antithrombin III inhibits thrombin and factors Xa, XIa, XIIa
and kallikrein.
Absence of antithrombin III leads to lack of inhibition, resulting in a hypercoagulable state.
Prothrombin 20210G-A
This mutation leads to increased plasma levels of prothrombin, predisposing to venous and possibly arterial thromboses.
Increased serum level of homocysteine predisposes to venous
and arterial thrombosis and to cardiovascular disease.
Antiphospholipid Antibodies
A heterozygous group of antibodies (IgM and IgG) directed
against protein-phospholipid complexes on which coagulation interactions occur, thereby interfering with normal coagulation cascade.
Two classes of antiphospholipid antibodies that currently
can be tested for:
Lupus anticoagulant
Anticardiolipin antibodies
Patients with these antibodies are at risk for venous and arterial thrombosis, recurrent spontaneous abortions, and neurologic complications.
Antiphospholipid antibodies may be idiopathic or associated with autoimmune diseases (e.g., systemic lupus erythematosus), drugs (e.g., hydralazine), or antiphospholipid
syndrome.
They are often associated with immune-mediated thrombocytopenia. Remember to check the platelets!
Symptomatic patients should be treated with warfarin, with
a goal INR of 2.5-3.5.
319
Lupus Anticoagulant
Initial tests to suggest lupus anticoagulantaPTT and
DRVVT, which do not correct with mixing.
Further testing (Fig. 2)
DRVVT corrects with addition of phospholipid.
Platelet neutralization procedureaPTT decreases by at
least 4 seconds with addition of platelets (source of phospholipid membranes).
Other tests (not routinely performed at Mayo Clinic)dilute
PT, kaolin clotting time, dilute tissue thromboplastin inhibition tests, factor Xa-activated aPTT, Taipan venom time
The patient should have at least two different tests (e.g.,
aPTT and DRVVT) to appropriately screen for lupus
anticoagulant.
Anticardiolipin Antibodies
These are a different type of antiphospholipid antibody and
must be tested for even if lupus anticoagulant screen is
negative.
The presence of anticardiolipin IgM or IgG is tested.
The significance of IgM antibodies is unclear.
The presence of IgM may be related to the acute process.
A positive test should be rechecked after the active disease
has resolved.
Deep Venous Thrombosis and Malignancy

Malignancy itself is an important risk factor for venous
thrombosis.
Hypercoagulability panel is not always indicated.
Does the history suggest another underlying hypercoagulable state?
Would it change your management and the length of anticoagulation?
320
aPTT and DRVVT

Abnormal
Thrombin time
Abnormal
Reptilase time
Mixing studies
Corrects
Factor deficiency
Factor
assays
Normal
No correction
Inhibitor
Heparin
PNP, DRVVT
(confirmatory tests)
Corrects
321
Lupus
anticoagulant
No correction
Specific factor
inhibitor
Abnormal
Fibrinogen
Fig. 2. Lupus anticoagulant screen.

DRVVT, dilute Russell viper venom
time; PNP, platelet neutralization
procedure.
Normal
HEPATITIS SEROLOGY
William Sanchez, M.D.
J. Eileen Hay, M.B.Ch.B.
EVALUATION
Evaluation with viral hepatitis serologic tests is reserved for
patients with known exposure or, more commonly, increased
serum levels of transaminases.
Definitionshepatitis A virus (HAV), hepatitis B virus
(HBV), hepatitis C virus (HCV), hepatitis D virus (HDV)
INDICATIONS
Evaluation of asymptomatic patients with increased serum
levels of transaminases
Evaluation of patients with symptoms suggestive of infectious
hepatitisfevers, jaundice, malaise, right upper quadrant
pain
Evaluation of the cause of chronic liver disease
Evaluation of patients with recent exposure to possible infectious sourceparenteral exposure, needlestick, high-risk
sexual contacts
Evaluation of immunity in patients vaccinated against viral
hepatitis
Evaluation of patients for transplant candidacy
INTERPRETATION
For interpretation of hepatitis serologic tests, see Table 1.
Hepatitis Amarkers include anti-HAV total and IgM
fraction
Hepatitis B
Special abbreviations used in this chapter: HAV, hepatitis A virus; HBcAg, hepatitis B core antigen; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface
antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HDV, hepatitis D virus.
323
Table 1. Interpretation of Hepatitis Serologic Tests

Disease state
Test results
Acute hepatitis A
Past exposure to
hepatitis A
Acute hepatitis B
(+) Anti-HAV IgM

(+) Anti-HAV IgG
Chronic hepatitis B
(high infectivity)
Chronic hepatitis B
(low infectivity)
Recovery from
acute hepatitis B
Vaccinated against
hepatitis B
Exposure to hepatitis C
Chronic hepatitis C
Active hepatitis D
(+) HBsAg
(+) Anti-HBcAg
(IgM)
(+) HBsAg
(+) Anti-HBcAg
(IgG)
(+) HBeAg
(+) HBsAg
(+) Anti-HBcAg
(IgG)
(+) Anti-HBeAg
(+) Anti-HBsAg
(+) Anti-HBcAg
(IgG)
() Anti-HBeAg
(+) Anti-HBsAg
(+) Anti-HCV
(+) Anti-HCV
(+) HCV-RNA
(+) Anti-HDV
Comments
Anti-HAV IgG confers
immunity
(+) HBeAg or (+) HBVDNA indicates high
infectivity
Anti-HBsAg IgG
confers immunity
If (+) by ELISA and

() by RIBA, consider
false positive
Anti-HCV is not protective against disease
Hepatitis D occurs only

as coinfection with
acute hepatitis B or as
superinfection on
chronic hepatitis B
HAV, hepatitis A virus; HBcAg, hepatitis B core antigen; HBeAg, hepatitis B

e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV,
hepatitis C virus; HDV, hepatitis D virus.
324
Markers include HBsAg (surface antigen), anti-HBsAg
HBcAg (core antigen), anti-HBcAg (total and IgM fraction)
HBeAg (e antigen, which indicates active viral replication), anti-HBeAg
HBV-DNA (also correlates with active viral replication)
Hepatitis C
Markers include anti-HCV by ELISA and RIBA
HCV-RNA by polymerase chain reaction
Hepatitis DMarkers include anti-HDV
ADDITIONAL TESTING
Evaluation of patients with high-risk exposure (high-risk
sexual contact, injection drug use, occupational needlesticks)
should include evaluation for HIV.
When evaluating chronic liver disease of unknown cause,
consider important differential diagnoses: occult alcohol
abuse, hemochromatosis (ferritin and iron studies), Wilson
disease (ceruloplasmin in patients <40 years), alpha1-antitrypsin deficiency (liver involvement can occur without
prominent pulmonary symptoms), autoimmune hepatitis
(antinuclear antibodies and other autoimmune markers).
Liver biopsy is indicated in chronic viral hepatitis for diagnosing cirrhosis.
Patients with chronic viral hepatitis are at increased risk for
hepatocellular carcinoma and should be screened with ultrasonography and serum alpha fetoprotein.
325
INTERPRETATION OF THE
ELECTROCARDIOGRAM
Nina Wokhlu, M.D.
Clarence Shub, M.D.
NORMAL ECG
Rapid and accurate ECG interpretation considered within
clinical context can result in appropriate lifesaving treatment.
ECG interpretation involves first and foremost determining
if a patient is clinically stable or unstable.
Unstable signs and symptoms are defined as shock,
hypotension (systolic blood pressure <90 mm Hg),
decreased consciousness or unresponsiveness, shallow or
absent respiration, thready or absent pulse, dyspnea, acute
pulmonary edema, chest discomfort, or myocardial
ischemia.
A normal ECG is labeled in Figure 1.
Normal Intervals
RR intervaltime between successive R waves on the ECG
PP intervaltime between successive P waves on the ECG
(this is the same as the RR interval on a normal ECG)
P waveinitial deflection, usually <0.11 second in duration and <2.5 mm tall
PR intervaltime between onset of the P wave and onset
of the QRS complex
Duration between 0.12 and 0.2 second
Duration inversely related to heart rate
QRS complextime from onset of the Q wave (or R wave
if no Q wave is present) to termination of the S wave
Normal duration, 0.06-0.1 second
Special abbreviations used in this chapter: APC, atrial premature contraction; AV,
atrioventricular; LAFB, left anterior-superior fascicular block; LBBB, left bundle branch block; LPFB, left posterior fascicular block; PVC, premature ventricular contraction; RBBB, right bundle branch block; SA, sinoatrial.
327
VAT
ST segment
10 mm = 1 mV
Voltage, mV
PR segment
T
P
U
J
PR interval
QS
Isoelectric line
QRS interval
QT interval
QU interval
1 mm
0
0.2
0.4
0.6
0.8
0.04
Time, second
Fig. 1. Normal ECG. VAT, ventricular activation time. (From

Goldschlager N, Goldman MJ. Principles of clinical electrocardiography. 13th ed. Norwalk [CT]: Appleton & Lange; 1989. Used with
permission.)
QT intervaltime from onset of the Q wave to termination

of the T wave
Duration should be less than half the preceding RR interval.
Corrected QT intervalQT interval (seconds)/square root
RR interval (seconds)
Usually 0.3-0.46 second
Inverse relation to heart rate
J pointpoint where the QRS complex ends and the ST segment begins
PR intervaltime from the end of the P wave to onset of
the QRS complex
ST segmentbegins after the J point and ends at the onset
of the T wave
Ventricular activation time (VAT)begins after onset of the
Q wave and ends at the R wave
328
U wavepositive deflection occasionally present after the T

wave and before the P wave
May be indicative of hypokalemia
ECG Determinations
Three main tasks
Determine if the Rhythm Is Regular or Irregular

If the distance between successive QRS complexes is constant, the rhythm is regular.
Determine if the QRS Complex Is Wide (>0.1 Second) or

Narrow
If the rhythm is regular, determine the origin: SA (sinoatrial) node, atrioventricular (AV) node (junctional), or ventricular (wide QRS complex).
Search for the P Wave
If the rhythm is irregular, determine the pattern of the irregularity.
Atrial fibrillationvarying RR intervals, nonexistent P
waves, or if P waves are present, they are abnormal with
varying P wave contours and variable PR intervals
Multifocal atrial tachycardiathree or more different P
wave morphologies with 1:1 conduction and a ventricular
rate 100 beats/minute
Wandering atrial pacemakerthree or more different P
wave morphologies with 1:1 conduction and a ventricular
rate <100 beats/minute
Atrial flutter with variable conduction (block)
Narrow Complex, Irregular Tachycardia

Common causes include atrial fibrillation, multifocal atrial
tachycardia, atrial flutter with variable conduction, and sinus
tachycardia with atrial premature contractions (APCs)
Ectopic Beats
Premature beats that occur out of synchrony with the baseline
rhythm (extrasystoles)
329
APC
Ectopic atrial contraction with a typical P-QRS-T morphology which occurs before the next anticipated sinus beat
There is often a compensatory pause after the APC before the
next normal beat.
An APC may also be nonconducted (isolated premature P
wave without a subsequent QRS).
Junctional Premature Contraction
Ectopic contraction originating in AV node with a narrow
QRS complex and no P wave or an inverted P wave (denoting retrograde conduction) preceding or following the QRS
complex
Best seen in leads II, III, and aVF
Premature Ventricular Contraction (PVC)

Ectopic ventricular contraction that occurs before the next
anticipated beat.
Characterized by a wide QRS morphology and no antecedent
P wave, or if a P wave is present, the PR interval will usually
be abnormal.
Ventricular bigeminya sinus beat alternates with a PVC
every other contraction
Ventricular trigeminyevery third beat is a PVC (ventricular quadrigeminy, every fourth beat is a PVC, and so
on)
Intrinsic Rates
SA node, 60-100 beats/minute
AV node, 40-60 beats/minute
Ventricular, 30-40 beats/minute
Rule of thumbdistance between QRS complexes incrementing by 1 large box = heart rate/minute: 300 150
100 75 60 50 43 37 beats/minute
When there is a regular, narrow QRS complex tachycardia at
a rate of 150 beats/minute, consider atrial flutter with 2:1
conduction.
A wide QRS complex tachycardia at a rate of 150
beats/minute is often ventricular tachycardia, but it could
reflect atrial flutter with 2:1 conduction and preexisting or
rate-related bundle branch block.
330
Association (or Dissociation) Between the P wave and
QRS Complex
Determine if the P wave is before or after or bears no relation to the QRS complex.
If every P wave is not followed by a QRS complex, secondor third-degree heart block (or atrial flutter) may be present.
QRS MORPHOLOGY AND QRS AXIS
Electrical axis is shown in Figure 2.
To calculate electrical axis in the frontal plane (net QRS
vector)
Measure the net positive or negative deflection (vector
sum the positive and negative components in relation to the
isoelectric line) of the QRS in lead I180 (negative
QRS) to 0 (positive QRS), then the same for aVF, 90
(negative QRS) to +90 (positive QRS)
Draw perpendicular lines to each axis at the appropriate
vector point.
A diagonal line from the center of the reference system to
the point where the two perpendicular lines intersect is
the axis in degrees.
Normal findings
The P wave, QRS complex, and T wave are all inverted in
lead aVR.
The P wave is upright in leads I, II, aVF, and most left-sided
precordial leads.
Note: An isolated Q wave in lead III may be a normal variant, but Q waves should not be seen in limb leads II and aVF;
in this case, an inferior infarct pattern should be considered.
Note: The QRS axis shifts leftward with increasing age.
Thus, a rightward or even vertical QRS axis in the elderly may be a clue to cardiac disease, e.g., pulmonary hypertension or conduction abnormality.
QRS Morphology
Bundle Branch Block
Reflects impairment in the left and/or right ventricular conduction system
331
332
90
120
60
aVR 150
30 aVL
Normal axis: +90 to 30

Left axis deviation: 90 to 30
180
0I
+150
+120
III
+30
+90
aVF
+60
II
Right axis deviation: +90 to 180

Extreme axis deviation 180 to 90
(often referred to as the Northwest
Quadrant)
Fig. 2. Electrical axis. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St.
Louis: Mosby; 2002. Used with permission.)
Complete bundle branch block results in a QRS complex
0.12 second in duration.
Incomplete bundle branch block pattern (or intraventricular conduction delay) results in an intermediate QRS
duration of 0.1-0.12 second.
Bundle branch block morphology in various leads is outlined in Table 1.
ECG features of left bundle branch block (LBBB) and right
bundle branch block (RBBB) are shown in Figures 3 and 4,
respectively.
The ECG in a patient with a pacemaker located in the right
ventricle (typical location) exhibits a pseudo-LBBB pattern.
Vertical pacemaker spikes immediately precede the atrial and ventricular impulses or just precede ventricular
impulses, depending on the type of pacemaker.
If a patient with a right ventricular pacemaker has an RBBB
(instead of the expected LBBB), consider ventricular septal perforation, with the tip of the pacing apparatus displaced
into the left ventricle.
Causes of bundle branch block include anteroseptal myocardial
infarction, Lev disease, Lengre disease (idiopathic degeneration of the cardiac conduction system), cardiomyopathy,
pulmonary embolism, pericarditis, and myocarditis.
Table 1. Bundle Branch Block Morphology in Various

Leads
Bundle branch block
Lead
I, aVL, V5-6
V1-2
Left
Monophasic wide positive
R wave
ST-segment depression
T-wave inversion
Deep, wide negative QS
or rS
Small r followed by deep,
wide S
Right
Small q wave
Tall R wave
Wide, slurred S wave
rSR' pattern
Possible ST-segment
depression
T-wave inversion
333
334
II
III
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
Fig. 3. ECG features of left

bundle branch block. (From
Huszar RJ. Basic dysrhythmias:
interpretation & management.
3rd ed. St. Louis: Mosby; 2002.
Used with permission.)
II
III
aVR
aVL
aVF
V1
V2
V3
V4
V5
V6
335
Fig. 4. ECG features of right bundle branch block. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St. Louis: Mosby; 2002. Used with permission.)
LBBB
May be persistent or rate-related
May be present only at faster heart rates (e.g., with
exercise)
May resolve as the heart rate returns to normal
Hemiblock denotes a fascicular conduction delay usually
with a near-normal QRS duration.
Left Anterior-Superior Fascicular Block (LAFB) Criteria

ECG features (Fig. 5)
Left axis deviation, 30 to 90
QRS duration <0.10 second, unless accompanied by other
blocks
Dominant R wave in leads I and aVL, with/without small
preceding q waves
Small R wave followed by a larger, deep S wave in leads
II, III, and aVF
Left Posterior Fascicular Block (LPFB)

ECG features (Fig. 6)
Right axis deviation, +90 to +180
QRS duration <0.10 second
Small R wave followed by deep S wave in leads I and
aVL
Small q wave followed by tall R wave in leads II, III, and
aVF
No evidence of right ventricular hypertrophy
Bifascicular Blocks
RBBB + LAFBQRS axis often between 60 and 120
RBBB + LPFBQRS axis often greater than +120
ECG findings are compared in Table 2.
Trifascicular Blocks
RBBB + LAFB + first-degree atrioventricular block (AVB)
RBBB + LPFB + first-degree AVB
Alternating RBBB and LBBB
Ventricular Hypertrophy
Left ventricular hypertrophy and right ventricular hypertrophy are compared in Figure 7.
336
II
III
aVR
aVL
aVF
Fig. 5. ECG features of left anter-
II
III
aVR
aVL
aVF
Fig. 6. ECG features of left posterior fascicular block. (From

Huszar RJ. Pocket guide to basic
dysrhythmias: interpretation and
management. 3rd ed. St. Louis:
Mosby; 2002. Used with permission.)
337
ior fascicular block. (From Huszar

RJ. Pocket guide to basic dysrhythmias: interpretation and
management. 3rd ed. St. Louis:
Table 2. ECG Findings in Bifascicular Block

ECG finding
QRS axis
Leads I, aVL
Leads II, III, aVF
Leads V1, V2
RBBB + LAFB
RBBB + LPFB
60 to 120
QR
RS
rSR'
+120
RS
QR
rSR'
LAFB, left anterior-superior fascicular block; LPFB, left posterior fascicular

block; RBBB, right bundle branch block.
Modified from Hoekstra JW. Handbook of cardiovascular emergencies. 2nd ed.
Philadelphia: Lippincott Williams & Wilkins; 2001. Used with permission.
Left Ventricular Hypertrophy Criteria

Precordial leads (Sokolow, Lyon criteria)
S wave in V1 + R wave in V5 (or V6) >35 mm
R wave in V5 or R wave in V6 >26 mm
R wave + S wave in any precordial lead >45 mm
Limb leads (Gubner, Ungerleider criteria)
R wave in lead I and S wave in lead III >26 mm
R wave in aVL >11 mm
S wave in aVR >15 mm
R wave in aVF >20 mm
Associated ST-segment depression and T-wave inversion in
leads with increased QRS voltage indicates left ventricular
hypertrophy with strain.
Note: There are multiple sets of criteria for diagnosing left
ventricular hypertrophy, such as the Sokolow, McPhie,
Cornell, and Estes criteria. No set has gained universal
acceptance. Sensitivity and specificity vary. QRS voltage criteria alone have reduced specificity. However, combining
QRS voltage criteria and repolarization criteria (left ventricular hypertrophy with strain) enhances specificity.
Right Ventricular Hypertrophy Criteria
Right axis deviation
R wave > S wave in V
1
qR pattern in V or V
1
3R
Pericardial Effusion/Tamponade
Electrical Alternans
A specific but not sensitive marker of a large pericardial
effusion with or without tamponade (Fig. 8)
338
V1
V6
Normal
LVH
RVH
or
or
Fig. 7. Right (RVH) and left (LVH) ventricular hypertrophy. The T

wave can be upright, flat, or inverted in lead V1 on a normal ECG.
(From Goldberger AL. Electrocardiography. In: Kasper DL, Braunwald
E, Fauci AS, Hauser SL, Longo DL, Jameson JL, editors. Harrisons
principles of internal medicine. Vol. II. 16th ed. New York: McGrawHill; 2002. p. 1315. Used with permission.)
339
It is related to excess motion of the heart within the pericardial sac, sometimes referred to as swinging heart.
The height of every other QRS complex alternately increases then decreases, often accompanied by low-voltage QRS
complexes.
Low QRS voltage is defined as <5 mm in the limb leads
and <10 mm in the precordial leads.
CARDIAC INJURY
Ischemia
ST-segment depression in contiguous leads, >1-2 mm with
downsloping or horizontal pattern (upsloping less diagnostic)
Measure ST-segment deviation 0.08 second after the J point.
Note: Although persistent ST-segment depression can be due
to ischemia, it has other causes, including left ventricular hypertrophy with strain, electrolyte disturbance, and digitalis effect.
Infarct
Terms ST elevation myocardial infarction and non-ST
elevation myocardial infarction are preferred (because it is
difficult to differentiate transmural from subendocardial
infarction by ECG criteria). The presence of Q waves implies
a greater degree of myocardial necrosis than the absence of
Q waves.
ST-Segment Configuration
Marked ST-segment elevation in two or more contiguous
ECG leads represents acute myocardial infarction.
Fig. 8. Electrical alternans. (From Goldberger AL. Electrocardiography.

In: Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS,
Kasper DL, editors. Harrisons principles of internal medicine. Vol. I.
13th ed. New York: McGraw-Hill; 1994. p. 954-66. Used with permission.)
340
Dynamic, transient ST-segment depression generally represents acute cardiac ischemia.

Always request a previous ECG for comparison.
Acute ST Elevation Myocardial Infarction

ECG criterionST-segment elevation 1-2 mm in two contiguous leads
During an acute ST elevation infarct, the ECG goes through
the following sequential changes (Fig. 9):
Early (seconds to minutes)T waves peak as large upright
hyperacute T waves (especially in anterior myocardial
infarction); T-wave inversions occur early as well.
This is followed within a short time (<30 minutes) by concave downward ST-segment elevation.
From 2 hours to days later, Q waves appear; T-wave inversions may persist or resolve completely months or years
later.
ST segment returns to baseline after a few days.
Note: Acute ST elevation may also be caused by transient
coronary artery spasm with transmural ischemia, which may
return to normal as the spasm is relieved and not necessarily cause infarction.
Other inciting causes of myocardial ischemia and acute ST
elevation include coronary artery dissection and cocaineinduced coronary spasm.
Where Is the Infarct?

A scheme for determining the location of an acute myocardial infarction is given in Figure 10.
Septal
Location: left anterior descending artery and its septal
perforators
Anterior
V3-V4 ST-segment elevation may be associated with poor
R-wave progression (decreasing or poorly increasing R
wave amplitude) in leads V2-V5
Location: left anterior descending artery and its diagonal
branches
341
342
a, Hyperacute T wave; b, inverted T wave
ST-segment elevation
Q wave
Fig. 9. Progression of myocardial infarction on ECG. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St.
II
III
aVR aVL aVF
V1
V2
V3
V4
V5
V6
Septal infarct
Lateral infarct
Extensive
anterior
infarct
Fig. 10. Scheme for determin-
Inferior infarct
Posterior infarct
ing the location of an acute

myocardial infarction on ECG.
(Modified from Huszar RJ. Basic
dysrhythmias: interpretation &
management. 2nd ed. St. Louis:
Mosby-Year Book; 1994. Used
with permission.)
343
Localized anterior infarct
Inferior
ST-segment elevation in leads II, III, and aVF, with reciprocal ST-segment depression in leads I and aVL
Location: right coronary artery and its posterior left ventricular branches or the left circumflex artery
Lateral
Leads I, aVL, and/or V5-V6 ST-segment elevation; reciprocal ST-segment depression in leads II, III, and aVF
V5-V6 ST-segment elevation may be combined with an
inferior infarct on ECG and is referred to as an inferolateral myocardial infarction.
Location: left circumflex artery and its obtuse marginal
branch or left anterior descending artery and its diagonal
branches
Posterior
Leads V1-V2 ST-segment depression, tall R waves in late
phase, not deep Q waves
Location: left circumflex artery and/or its posterolateral
branch
Right ventricle
V2R-V4R ST-segment elevation, occasionally V1-V3
Location: right coronary artery
Diagnosis of Myocardial Infarction in the Presence of LBBB

Can be challenging
ECG features are shown in Figure 11.
Scoring system to aid in diagnosis of acute myocardial infarction confounded by LBBB on ECG
Score >3 suggests acute infarction.
ST-segment elevation 1 mm concordant (the same direction) with the QRS complex is highly suggestive of infarction (score of 5).
ST-segment depression 1 mm in leads V1, V2, or V3 is
highly suggestive of infarction (score of 3).
ST-segment elevation 5 mm discordant (opposite direction)
with the QRS complex is suggestive of infarction (score of 2).
ST-Segment Elevation
Can be associated with coronary artery vasospasm, myocarditis, pericarditis, ventricular aneurysm, and, less frequently,
with Brugada syndrome
344
aVR
V1
II
aVL
III
aVF
V4
V5
345
Fig. 11. Acute myocardial

infarction with left bundle
branch block. This patient
meets all three criteria: concordant ST-segment elevation (lead II), ST-segment
depression in leads V1, V2,
or V3 (leads V2 and V3), and
discordant ST-segment elevation (leads III and aVF).
(From Sgarbossa EB, Pinski
SL, Barbagelata A, Underwood DA, Gates KB, Topol
EJ, et al., GUSTO-1 Investigators. Electrocardiographic
diagnosis of evolving acute
myocardial infarction in the
presence of left bundlebranch block. N Engl J
Med. 1996;334:481-7. Used
with permission.)
Brugada syndromea pattern of ST-segment elevation in

leads V1, V2, and V3 with coexisting RBBB
This pattern can be a marker for sudden death (Fig. 12).
ST-segment elevation is transient with coronary spasm,
myocarditis, and pericarditis.
Persistent ST-segment elevation >1 month after infarction
may signal the possibility of ventricular aneurysm.
Pericarditis
Diffuse concave upward ST-segment elevation associated
with PR segment depression (Fig. 13)
Reciprocal depression of ST segment in aVR
T-Wave Abnormalities
T-wave inversions (similar to ST-segment depression) can
indicate cardiac ischemia if they are in two or more contiguous leads, especially if they are symmetric, new, and
correspond clinically to time of occurrence of chest pain.
Tall, peaked T waves, particularly in the precordial leads,
can also indicate hyperkalemia.
Q Waves
Pathologic Q waves in contiguous leads indicate completed
transmural infarct, referred to as a Q-wave infarct.
Pathologic Q waves are at least 1/4 the height of the succeeding QRS complex and are at least 0.04 second in duration.
The distribution of the Q waves on the ECG leads indicates
the location of the transmural infarct (e.g., anterior, anterolateral, inferior, inferolateral). Multiple Q-wave infarcts
may be present.
Abnormal P Wave Morphology

May indicate right or left atrial enlargement (Fig. 14)
Left atrial enlargement
Broad, notched P waves (P mitrale) often seen in lead II
Biphasic P waves in V1 (positive then negative deflection)
Right atrial enlargement
Tall, peaked P waves >2.5 mm in leads II, III, and aVF
(P pulmonale)
Cardiac Conduction Disturbances

SA node exit block
346
I
aVR
II
aVL
III
aVF
V1
V4
V2
Fig. 12. Brugada syndrome. ECG of a 32-year-old man who had

cardiac arrest without evidence of structural heart disease. (From
Brugada J, Brugada R, Brugada P. Right bundle-branch block and STsegment elevation in leads V1 through V3: a marker for sudden death
in patients without demonstrable structural heart disease. Circulation.
1998;97:457-60. Used with permission.)
347
348
aVR
V1
V4
II
aVL
V2
V5
III
aVF
V3
V6
Fig. 13. Pericarditis. Note the classic signs of diffuse concave upward ST-segment elevation
with concomitant PR depression. (From Oh JK. Pericardial diseases. In: Murphy JG, editor.
Mayo Clinic cardiology board review. 2nd ed. Philadelphia: Lippincott Williams & Wilkins;
2000. p. 509-32. By permission of Mayo Foundation for Medical Education and Research.)
ECG lead II
ECG lead V1
P pulmonale
349
Fig. 14. P-wave morphology in atrial enlargement. (From Swanton RH. Cardiology. 5th ed. Oxford:
Blackwell Publishing; 2003. Used with permission.)
P mitrale
Caused by a block in conduction between the SA node

and the atria, resulting in the omission of a complete PQRS-T complex (Fig. 15)
A long pause occurs that is a multiple of the PP interval of
the predominant rhythm.
SA node (Wenckebach)
A cyclical decrease in the PP interval until a P wave is
omitted
PR interval is constant.
Sinus arrest
Caused by failure of the SA node
Standstill of the heart for 1.6-2.0 seconds (Fig. 16)
No P wave is generated.
A long pause occurs that is not a multiple of the PP cycle.
First-degree AV block
Sinus rhythm (Fig. 17)
PR interval 0.2 second constant from contraction to
contraction.
Second-degree AV block
Mobitz I (Wenckebach)
Progressive prolongation of the PR interval with eventual omission of the QRS complex with repetition of
the same cycle (Fig. 18)
Shortened PR interval succeeding the nonconducted
QRS complex
Characterized by progressive decrease in the RR interval
Mobitz II
Fixed PR interval with eventual omission of the QRS
complex in a cyclical pattern: often 2:1 (i.e., two cycles
of conducted QRS to 1 omitted QRS), 3:1, 3:2, or 4:1,
etc. (Fig. 19)
Third-degree, or complete, heart block
Atrial impulses are completely blocked with two independent rates: an atrial rate and an autonomous slow ventricular rate (Fig. 20).
QRS complexes may be narrow at a rate of about 50-60
beats/minute if the AV junction is the source of ventricular impulses or wide if the origin is below the AV junction,
i.e., idioventricular, at a rate of usually <45 beats/minute.
Causes of complete heart block include myocardial infarction, conduction disease of the elderly, Lyme disease,
350
351
Fig. 16. Sinus arrest. (From Swanton RH. Cardiology. 5th ed. Oxford: Blackwell Publishing; 2003. Used with permission.)
Fig. 15. Sinoatrial node exit block. Note that the period of exit block is a multiple (twice) of the previous PP interval. (From
Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St. Louis: Mosby; 2002. Used with permission.)
Chagas disease, digitalis toxicity, infiltrative disease (e.g.,

amyloidosis), infective endocarditis, and other, miscellaneous rare diseases.
DISTURBANCES OF RATE
Tachy-brady syndrome
A form of sick sinus syndrome or sinus node dysfunction (Fig. 21)
Definitionperiods of alternating tachycardia and bradycardia.
Bradyarrhythmias
Sinus bradycardia
Sinus rhythm (normal P-QRS-T configuration) with a
heart rate <60 beats/minute (Fig. 22)
AV junctional rhythm
Regular narrow complex QRS rhythm at a rate of 40-60
beats/minute with no P waves or visible retrograde P waves
in leads II, III, and aVF (Fig. 23)
Accelerated junctional rhythm
Regular narrow complex QRS rhythm at a rate of 60-100
beats/minute with no P waves (Fig. 24)
Retrograde P waves preceding or succeeding the QRS in
leads II, III, and aVF may occur.
Idioventricular rhythm
Wide QRS complex, regular (or rarely irregular) ventricular-based rhythm (Fig. 25)
Rate, 30-40 beats/minute
Accelerated idioventricular rhythm
Ventricular-based rate at 60-120 beats/minute
Note broad QRS complexes without P waves in Figure
26.
Also referred to as slow ventricular tachycardia
Tachyarrhythmias
Sinus tachycardia
Sinus rhythm (normal P-QRS-T configuration) at a heart
rate >100 beats/minute
Atrial flutter
Rapid atrial rate of 250-350 beats/minute with various
degrees of AV conduction delay
352
gencies: a pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
353
Fig. 18. Mobitz I (Wenckebach) atrioventricular block. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a
pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Fig. 17. First-degree atrioventricular block. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emer-
354
Fig. 19. Mobitz II atrioventricular block. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket guide. Oxford:
Butterworth-Heinemann; 1998. Used with permission.)
Fig. 20. Third-degree heart block. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket guide.
Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Philadelphia: Current Medicine, Inc.; 1997. p. 6.1-6.36. Used with permission.)
355
Fig. 22. Sinus bradycardia at a rate of 30 beats/minute. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a
pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Fig. 21. Sick sinus syndrome. (From Scheinman M. Arrhythmias. In: Braunwald E, editor. Essential atlas of heart diseases.
356
Fig. 23. Junctional rhythm. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St. Louis: Mosby;
2002. Used with permission.)
Fig. 24. Accelerated junctional rhythm. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St. Louis:
357
Fig. 25. Idioventricular rhythm. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St. Louis:
The sawtooth pattern of P waves in classic atrial flutter

is seen best in leads II, III, and aVF.
AV conduction delays often 2:1, 3:1, 4:1, or variable conduction delay (Fig. 27)
Atrial fibrillation
Completely irregular atrial activity resulting in no discernable or consistent P waves, with resultant irregular
ventricular activity (Fig. 28)
If the ventricular rate is 100 beats/minute, it is said to
be atrial fibrillation with rapid ventricular response.
Paroxysmal supraventricular tachycardia
Atrial rate of 150-250 beats/minute (Fig. 29)
Narrow QRS complexes
Atrial P waves vary with at least three different P wave
morphologies (and origins) at a rate 110/minute, thus
resulting in an irregular ventricular rate (Fig. 30).
Ectopic P waves are seen best in leads II, III, and aVF.
It often coincides with severe pulmonary disease.
Junctional tachycardia
Morphologic features similar to those of a junctional rhythm,
with a faster ventricular rate, usually >100/minute (Fig. 31)
Three or more ventricular depolarizations at a rate of 100200 beats/minute, with QRS >0.12 second
QRS may be uniform (unifocal) or multiform (multifocal).
AV dissociation may be found.
Left axis deviation is common but not universal.
Sustained ventricular tachycardia is present when the duration is at least 30 seconds (Fig. 32).
Note: The presence of AV dissociation suggests that a wide
complex tachycardia is ventricular in origin.
Note: Ventricular tachycardia should be regular or nearly so.
If it is irregular, then suspect atrial fibrillation or atrial flutter with
(rate-related) aberrancy or underlying bundle branch block.
Torsades de pointes
A form of polymorphic ventricular tachycardia in which
the axis of the QRS complex changes direction in a cyclic
fashion (Fig. 33).
Often preceded by a rhythm with a prolonged QT interval
358
guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
359
Fig. 27. Atrial flutter with 3:1 block. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket guide.
Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Fig. 26. Accelerated idioventricular rhythm. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket
360
Fig. 28. Atrial fibrillation. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket guide. Oxford:
Fig. 29. Paroxysmal supraventricular tachycardia. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket
guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
361
Fig. 31. Junctional tachycardia. (From Huszar RJ. Basic dysrhythmias: interpretation & management. 3rd ed. St.
Fig. 30. Multifocal atrial tachycardia. Varying P-wave morphologies are present with varying RR interval. (From Xie B, Thakur
RK, Shah CP, Hoon VK. Clinical differentiation of narrow QRS complex tachycardias. Emerg Med Clin North Am. 1998;16:295330. Used with permission.)
362
Fig. 32. Sustained monomorphic ventricular tachycardia. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies:
a pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Fig. 33. Torsades des pointes. Note how the QRS axis appears to rotate about an isoelectric line. (From Nolan J, Greenwood
J, Mackintosh A. Cardiac emergencies: a pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Tachyarrhythmias with a wide QRS represent ventricular

tachycardia or supraventricular tachycardia with aberrancy
or previous bundle branch block (Table 3)
Factors favoring ventricular tachycardia include
QRS duration >0.12 millisecond
The likelihood improves further if the QRS duration >0.14
millisecond and RBBB morphology or QRS >0.16 millisecond and LBBB morphology
Table 3. Comparison of Ventricular Tachycardia and

Supraventricular Tachycardia
Factor
Ventricular
tachycardia
Supraventricular
tachycardia
Rate/minute
Usually 100-200
Usually 150-250
beats/minute
beats/minute
100-130
13% of patients
1% of patients
130-170
47% of patients
27% of patients
170-200
21% of patients
60% of patients
>200
19% of patients
12% of patients
Relation of P
AV dissociation
1:1 P:QRS ratio (if P
waves to QRS
Only 33% of patients waves are visible)
complex
show a 1:1 P:QRS
100% of patients
ratio
QRS duration, Wide complex
Wide or narrow
milliseconds
<120
14% of patients
76% of patients
120-140
19% of patients
24% of patients
>140
67% of patients
0% of patients
Relation of
Similar morphology
Usually different
QRS to
morphology unless
previous
bundle branch block
premature
was previously present
contractions
Capture or
Yes (may be observed) No (not observed)
fusion beats
AV, atrioventricular.
Modified from Shen W-K, Hammill SC. Cardiac arrhythmias. C.
Ventricular arrhythmias. In: Giuliani ER, Gersh BJ, McGoon MD, Hayes
DL, Schaff HV, editors. Mayo Clinic practice of cardiology. 3rd ed. St.
Louis: Mosby; 1996. p. 780-820. By permission of Mayo Foundation.
363
Left axis deviation, QRS morphology similar to previous

PVCs, capture and fusion beats.
Ventricular tachycardia characteristically may demonstrate fusion
or capture beats, especially at relatively slow rates (Fig. 34).
A fusion beat results from merging simultaneous supraventricular and ventricular impulses, producing a QRS complex of intermediate morphology compared with the
supraventricular and ventricular impulses.
A capture beat occurs when an atrial impulse passes
through the AV node, with a resultant narrow QRS complex that is clearly different from the predominant QRS
morphology in a wide complex tachycardia.
Ventricular fibrillation
Unstable, disorganized ventricular electrical activity (Fig. 35)
Rate >300 beats/minute with QRS waveforms of variable
width and regularity.
Ventricular asystole
Flatline, absence of ventricular activity (Fig. 36)
Preexcitation Syndromes
Wolff-Parkinson-White syndrome
A triad of short PR interval 0.11 second, widening of the
QRS complex (0.11 second), and slurring of the first
portion (upstroke) of the QRS complex (known as the
delta wave, which is referred to as preexcitation)
(Fig. 37)
Complicated by episodes of supraventricular tachycardia
that can be either wide or narrow complex, depending on
the conduction pathway.
Lown-Ganong-Levine syndrome
PR interval <0.12 second, with a QRS complex of normal duration associated with paroxysmal supraventricular tachycardia
364
365
Fig. 34. Confirming the diagnosis of ventricular tachycardia. Fusion beats (solid arrows) and capture
beats (open arrows) are shown. (From Brady WJ, Skiles J. Wide QRS complex tachycardia: ECG differential diagnosis. Am J Emerg Med. 1999;17:376-81. Used with permission.)
366
Fig. 35. Ventricular fibrillation. Note the chaotic ventricular activity. (From Nolan J, Greenwood J, Mackintosh A. Cardiac
emergencies: a pocket guide. Oxford: Butterworth-Heinemann; 1998. Used with permission.)
Fig. 36. Asystole. (From Nolan J, Greenwood J, Mackintosh A. Cardiac emergencies: a pocket guide. Oxford:
Electrolyte- and Medication-Induced Arrhythmias
Hyperkalemia
Tall, narrow peaked T waves particularly prominent in
the precordial leadsP waves disappearQRS complexes widen resembling a sine wave (progressive
increase in serum potassium) (Fig. 38)
Hypokalemia
Prominent U wave, amplitude >1.5 mm (may be larger
than the T wave) (Fig. 39)
Prolonged QT interval
May be caused by hypocalcemia, hypomagnesemia, bradyarrhythmias, amiodarone, sotalol, tricyclic antidepressants, type IA antiarrhythmic agents, phenothiazines, liquid-protein diets, and congenital prolonged QT syndromes
(Romano-Ward syndrome [associated with normal hearing] and Jervell and Lange-Nielsen syndrome [associated
with deafness]) (Fig. 40)
Note: Prolonged QT interval predisposes toward ventricular
tachycardia, particularly torsades des pointes. The treatment
of choice is often to discontinue any offending medication.
Digitalis toxicity
Characteristic concave upward scooped ST segment,
lengthened PR interval or higher degrees of AV block, SA
block, paroxysmal atrial tachycardia, sinus bradycardia,
PVCs, ventricular tachycardia, ventricular fibrillation,
junctional rhythm, or junctional tachycardia (Fig. 41)
367
368
III
Fig. 37. Wolff-Parkinson-White syndrome. (Modified from OKeefe JH Jr, Hammill SC, Freed MS, Pogwizd SM. The complete guide to ECGs. 2nd ed. Royal Oak [MI]: Physicians Press; 2002. Used with permission.)
V4
V5
II
III
Fig. 38. Top, Moderate hyperkalemia (leads V3-V5). Bottom, Severe hyperkalemia (leads I-III).
369
(From Swanton RH. Cardiology. 5th ed. Oxford: Blackwell Publishing; 2003. Used with permission.)
V3
370
T wave U wave
Fig. 39. Hypokalemia. Note the prominent U wave. (From Thaler MS. The only EKG book youll
ever need. 4th ed. Philadelphia: Lippinicott Williams & Wilkins; 2003. Used with permission.)
Fig. 41. Digitalis effect. Note upward concavity of the ST segments. (Modified from OKeefe JH Jr,
371
Hammill SC, Freed MS, Pogwizd SM. The complete guide to ECGs. 2nd ed. Royal Oak [MI]:
Physicians Press; 2002. Used with permission.)
Fig. 40. Prolonged QT interval. Corrected QT interval was 0.5 second. (Modified from OKeefe JH Jr,
Hammill SC, Freed MS, Pogwizd SM. The complete guide to ECGs. 2nd ed. Royal Oak [MI]: Physicians
Press; 2002. Used with permission.)
LIVER FUNCTION TESTS
Jason Persoff, M.D.
Stephen M. Lange, M.D.
EVALUATION OF LIVER FUNCTION
Several lab tests evaluate the presence of liver damage or
impairment of liver function. These tests are loosely termed
liver function tests.
It can be helpful to subcategorize liver function tests to reflect
specific patterns of liver injury:
Markers of cholestasis
Markers of hepatocellular injury
Markers of biosynthetic function
Commonly used liver function tests and their normal values
are listed in Table 1.
Normal values can vary with age, sex, ethnicity, and body
mass index and are determined by the lab of each institution.
INDICATIONS
Liver function tests generally are ordered for the following
reasons:
To detect hepatobiliary disease
To estimate the degree of injury to the liver
As an indirect or direct measure of abnormality in other
organ systems, as in pancreatitis, metastatic cancer, acute
myocardial infarction, myopathy, right heart failure,
encephalopathy, hemolysis, and shock states
To monitor for adverse drug effects
As a general screen for critically ill patients
Some indications for which liver function tests may be helpful are listed in Table 2.
Special abbreviation used in this chapter: ALP, alkaline phosphatase.

373
Table 1. Normal Values for Liver Function Tests

Test
Marker of hepatocellular
injury
AST*
ALT
Markers of cholestasis
Bilirubin
Total
Direct (conjugated)
Normal value
12-31 U/L
Male, 10-45 U/L
Female, 9-29 U/L
0.1-1.1 mg/dL
0-0.3 mg/dL (20%-50% of total
bilirubin)
ALP
Male, 98-251 U/L Female, 81-312 U/L
Liver isoenzyme
24-158 U/L
Bone isoenzyme
24-146 U/L
Intestine isoenzyme 0-22 U/L
GGT
8-48 U/L
5NT
4.0-11.5 U/L
Markers of biosynthetic
function
Albumin
3.5-5 g/dL
PT
8.4-12 seconds
ALP, alkaline phosphatase; GGT, -glutamyltransferase; 5NT, 5'-nucleotidase.

*Also called SGOT (serum glutamic-oxaloacetic transaminase).
Also called SGPT (serum glutamic-pyruvic transaminase).
Operating characteristics for identifying specific disease

states are described in Table 3.
INTERPRETATION
The approach to the interpretation of abnormal liver function
tests should be guided by the following three important principles:
Liver function tests are sensitive markers of hepatobiliary
disease.
Not all liver function test abnormalities reflect abnormalities of the hepatobiliary system.
Additional testing is often required to confirm a specific
diagnosis.
Liver function test abnormalities and the corresponding conditions are given in Table 4.
Cholestasis of any cause is best suggested by abnormalities
374
Table 2. Indications for Liver Function Tests
Clinical indications
Jaundice (total
bilirubin
>2.5 mg/dL)
Ascites
Tender hepatomegaly
Abdominal pain
(Murphy sign)
Risk for viral
hepatitis
Risk for primary
liver neoplasm
Suggestive family
medical history
(e.g., hemochromatosis)
Suspected cholangitis
Dark urine
Known toxic
ingestions
Suicide attempts
Encephalopathy,
seizures, coma
Nonspecific malaise
Nonhepatobiliary
indications
Drug effects &

monitoring
for toxicity*
Pancreatitis
Examples
Heart failure
HMG-CoA
Constrictive
reductase
pericarditis
inhibitors
ThiazolidinePremature
diones
emphysema
Methotrexate
Metastatic disease
Isoniazid
Myopathies
Amiodarone
Autoimmune
Anticonvuldisorders
sants
Inflammatory bowel Others
disease
NSAIDs
Sepsis
ACE-inhibitors
Bone disorders
Nicotinic acid
Diabetes mellitus
Sulfonamides
Skin pigmentation
Erythromycin
Kayser-Fleischer
Griseofulvin
ring
Fluconazole
Chondrocalcinosis
(pseudogout)
Hemolysis
ACE, angiotensin-converting enzyme.

*Regular toxicity monitoring is recommended for few select drugs.
in alkaline phosphatase (ALP) and bilirubin (primarily direct

bilirubin) out of proportion to the aminotransferases.
A marked increase in bilirubin (>25-30 mg/dL) is more suggestive of hepatocellular injury than extrahepatic cholestasis. An increase >15 mg/dL itself usually requires a concomitant hemolytic process or renal insufficiency in addition to hepatocellular injury.
In Gilbert syndrome and hemolysis, total bilirubin is usually
<6 mg/dL.
375
376
Table 3. Operating Characteristics for Identifying Specific Disease States

Disease
Test
Characteristics
Sensitivity, %
Obstructive jaundice
Direct bilirubin >50% of

total bilirubin
ALP >3 normal
+LHR
AST, U/L
200
201-400
401-600
601-1,000
>1,000
ALP <2 normal
AST:ALT <1
1.4
32
0.16
85
2.4
65
0.23
99
73
57
50
28
90
90
AST:ALT
>2
>3
ALP, alkaline phosphatase; LHR, likelihood ratio.
Specificity, %
81
98
99
>99
100
77
Positive predictive value, %

Alcohol-induced injury
LHR
95
Sensitivity, %
Acute viral hepatitis
Specificity, %
90
96
LHR
0.4
1.0
7.0
20.0
Table 4. Abnormal Liver Function Tests
Values
Test
AST
Increased
Hepatocellular necrosis
(very high levels)
Acute viral hepatitis
Microsteatosis
Reye syndrome
Acute fatty liver of
pregnancy
Liver disease of any cause
Cirrhosis
Hepatic ischemia
Nonalcoholic steatohepatitis
Biliary disease
Heart failure
Neoplasms
Granulomas
Musculoskeletal injury
IM injections
Myoglobinuria
Myopathies
Pancreatitis
Intestinal injury
Radiation injury
Cerebral infarction
Renal infarction
Drugs & herbal preparations
Burns
Mushroom poisoning
Lead poisoning
Hemolytic anemia
Myopathies
Trichinosis
Macroenzyme AST
Decreased
Azotemia
Chronic renal dialysis
Pyridoxal phosphate
deficiency states
Less so than with ALT
(See ALT for associated conditions)
377
Table 4 (continued)
Values
Test
ALT
Increased
Tends to parallel AST,
but lower in alcoholic
liver disease
Obesity
Severe preeclampsia
Rapid progressive acute
lymphoblastic leukemia
Bilirubin Hepatic & posthepatic

jaundice
Prolonged fasting
Direct bilirubin
Biliary obstruction
(especially posthepatic)
Dubin-Johnson
syndrome
Rotor syndrome
Indirect bilirubin
Hemolysis
Gilbert disease
Crigler-Najjar
syndrome
Drugs
Novobiocin
Thyrotoxicosis
Large hematomas
ALP
Bone
Hyperparathyroidism
Paget disease
Tumors & bony
metastasis
Osteomalacia, rickets
Hyperthyroidism
Extensive fractures
(healing phase)
Osteogenesis
imperfecta
378
Decreased
Genitourinary tract
infections
Malnutrition
Pyridoxal phosphate
deficiency states
Alcoholic liver disease
Pregnancy
Malnutrition
Certain drug ingestions
Barbiturates
Excess vitamin D
Milk-alkalai syndrome
Hypothyroidism, cretinism
Pernicious anemia
Celiac disease
Malnutrition
Scurvy
Zinc deficiency
Magnesium deficiency
Congenital hypophosphatasia
Table 4 (continued)
Values
Test
Increased
Decreased
ALP (continued)
Liver
Biliary obstruction of
any cause
Hyperthyroidism
Diabetes mellitus
Neoplasms
Hepatic venous
congestion
Adverse drug toxicity
Infiltrative (amyloidosis,
leukemia)
Liver disease
Acute hepatitis
Cirrhosis
Primary biliary
cirrhosis
Hepatosteatosis
Intestine
Inflammatory bowel
disease
Severe malabsorption
Intestinal infarction
Chronic hemodialysis
Others
Hyperphosphatasia
Ectopic production
from tumors
Ovarian, cervical
cancer
Vascular endothelial
origin
Children
Pregnancy (placental
isoenzyme)
Type O & B blood
after fatty meal
379
Table 4 (continued)
Values
Test
GGT*
5NT
Albumin
380
Increased
Alcohol
Alcoholic hepatitis
Biliary obstruction
Acute pancreatitis
Liver metastasis
Nonhepatic neoplasms
Hypernephroma,
melanoma, lung,
breast
Acute hepatitis
Chronic active hepatitis
Cirrhosis
Primary biliary cirrhosis
Fatty liver
Acute myocardial
infarction
Drug effects
Hyperthyroidism
Biliary obstruction of
any cause
Liver metastasis (often
preceding jaundice)
Hepatoma
Dehydration
IV albumin infusions
Decreased
Hypothyroidism
Malnutrition
Malabsorption syndromes
Hyperthyroidism
Pregnancy
Liver disease (decreased
synthesis)
Chronic infection
Hereditary analbuminemia
Neoplasms
Nephrotic syndrome
Protein-losing enteropathy
Dilutional
Iatrogenic, SIADH,
polydipsia
Congenital deficiency
Hemorrhage
Burns
Crohn disease
Table 4 (continued)
Values
Test
PT
Increased
Decreased
Factor deficiency or defect Ovarian hyperfunction

I (fibrinogen), II
Regional enteritis or
(prothrombin), V,
ileitis
VII, X
Inadequate vitamin K
Fat malabsorption
Severe liver damage (decreased factor synthesis)
Drugs
Warfarin
Idiopathic familial hypoprothrombinemia
Circulating anticoagulants
Systemic lupus
erythematosus
Hypofibrinogenemia
(factor I)
Acquired or inherited
Zollinger-Ellison syndrome
Hypervitaminosis
ALP, alkaline phosphatase; GGT, -glutamyltransferase; SIADH, syndrome

of inappropriate antidiuretic hormone.
*Normal in pregnancy and postpartum states as well as in bone diseases,
unlike ALP.
Normal in pregnancy and postpartum states, unlike ALP.
Data from Wallach J. Interpretation of diagnostic tests. 7th ed. Philadelphia:
Lippincott Williams & Wilkins; 2000.
The hepatobiliary origin of ALP can be confirmed by an

increase in the liver isoenzyme of ALP, 5'-nucleotidase, or glutamyltransferase.
ALT is more specific to the liver than AST, and an increase
in AST alone should prompt evaluation for a nonhepatobiliary cause of the AST abnormality (e.g., in a patient with a
history of chest pain, consider acute myocardial infarction).
381
An increased AST:ALT ratio >2 is more suggestive of alcohol-induced liver disease (this stems from an alcohol-induced
pyridoxal phosphate deficiency). AST does not usually
exceed 250 U/L when related to alcoholic hepatitis.
However, the AST:ALT ratio also increases (i.e., >1) with
increasing degrees of hepatic fibrosis and cirrhosis.
An AST:ALT ratio <1 is more suggestive of viral hepatitis in
an acutely jaundiced patient, whereas in an asymptomatic
patient, it likely is a reflection of nonalcoholic steatohepatitis.
Extreme increases in aminotransferase levels (Table 3) are
most specific for, and thus suggestive of, the diagnosis of
acute viral hepatitis, but they also can occur with acute drug
toxicity or shock. (However, sensitivity at these levels diminish, and lower levels should not preclude the physician from
considering these diagnoses.)
The accumulated damage to the liver cannot be gauged by
AST, ALT, ALP, or bilirubins alone. PT or albumin reflects
the biosynthetic capacity of the liver and is a better marker
of the degree of liver function in acute liver failure or chronic liver disease. Factor levels, such as factor V, can test for
this more directly.
ADDITIONAL TESTING
Depending on the specific clinical scenario, additional testing may be indicated to define the specific hepatobiliary or
even possibly extrahepatobiliary cause of abnormal liver
function tests. Other tests that are often used to follow up an
initially abnormal liver test profile are listed in Table 5.
An initial algorithmic approach to abnormal liver function
tests is more appropriate for outpatients than hospitalized
patients. For patients who are primarily asymptomatic but
have increased AST or ALP, Figures 1 and 2 give two algorithms for the appropriate work-up.
382
Table 5. Additional Tests to Consider

Tests
Viral hepatitis serologies
Serum ceruloplasmin
24-hour urine copper
Serum copper
Serum protein electrophoresis
Suggested diagnosis
Viral hepatitis
Hemochromatosis
Wilson disease
1-Antitrypsin deficiency
Decrease in 1-globulin band
Autoimmune hepatitis
Increase in polyclonal immunoglobulin
383
Transferrin saturation
Iron saturation/TIBC
HFE gene mutation
Possible clinical features

Acute febrile illness, predisposing risk
factors (IV drug abuse, travel),
asymptomatic, vasculitis
Family history, diabetes, skin pigmentation,
cardiomyopathy, hypogonadism, pseudogout & chondrocalcinosis, hypothyroidism,
liver disease
Kayser-Fleischer rings, family history, <30
years old, risus sardonicus, cognitive
impairment, bradykinesia, rigidity, ataxia,
tremor, liver disease (can present as acute
liver failure)
Panacinar emphysema, panniculitis,
liver disease, family history
Asymptomatic to fulminant liver
disease, other autoimmune disorders
384
Table 5 (continued)
Tests
1-Antitrypsin
Phenotype
Serum levels
Antiendomysial & antigliadin
antibodies
Antimitochondrial antibodies
CK/aldolase
Troponin
Echocardiography
Suggested diagnosis
(As above)
Diarrhea, weight loss, anemia, osteomalacia,

ataxia, depression, epilepsy, arthritis,
dermatitis herpetiformis, autoimmune
disorders
Asymptomatic to advanced cholestatic liver
disease, fatigue, pruritis, younger woman,
hyperpigmentation (not due to jaundice)
Weakness, Gottron papules, dermatoheliosis,
significant muscle trauma, drug-induced
myositis, underlying malignancy
Chest pain, history of atherosclerotic disease
Congestive heart failure, right-sided heart
failure, pericardial calcifications, Kussmaul
sign, prominent liver pulsations, murmur of
tricuspid regurgitation, elevated ascitic total
protein with portal hypertension
Celiac sprue
Primary biliary cirrhosis
Muscle injury & inflammation
Causes of cardiac cirrhosis
Table 5 (continued)
Tests
Imaging
Ultrasound, CT, MRI
ERCP
Liver biopsy
Suggested diagnosis
(As above)
Critically ill patients, history of depression,

history of drug or alcohol abuse
(As per specific diagnoses)
Important in acute liver failure

Acetaminophen, alcohol, coingestions
Steatosis, masses, hepatic/portal vein
thrombosis, cholelithiasis & related
diseases, granulomas, abscesses, infiltrative
processes, primary sclerosing cholangitis
Often definitive at determining cause of
liver lesion & at staging the extent of
liver damage
Not indicated in acute liver failure
(fulminant hepatitis)
(As per specific diagnoses)
ERCP, endoscopic retrograde cholangiopancreatography; TIBC, total iron-binding capacity.
385
Antinuclear antibodies &

anti-smooth muscle
antibodies
Toxicology screen
386
AST elevated
ALT elevated
Pursue nonhepatobiliary
causes of AST elevation
No
Yes
ALT >3-5x normal
No
Symptomatic or elevated
total bilirubin, ALP or ALT
elevated >6 months
Yes
Yes
No
Recheck 3-6 months
Investigate for liver disease

ANA, AMA, ceruloplasmin, transferrin saturation, SPEP,
hepatobiliary sonogram, liver biopsy
Fig. 1. Increased AST level in a

well patient. ALP, alkaline phosphatase; AMA, antimitochondrial
antibody; ANA, antinuclear antibodies; SPEP, serum protein electrophoresis. (Modified from Kamath
PS. Clinical approach to the patient
with abnormal liver tests. Mayo Clin
Proc. 1996;71:1089-95. By permission of Mayo Foundation for
Medical Education and Research.)
ALP elevated
Fig. 2. Increased alkaline
Nonhepatic causes
No
Yes
ALP >2x normal
No
Yes
Symptomatic or ALP
elevated >6 months
No
Recheck 3-6 months
Yes
Dilated bile ducts

by ultrasound
No
AMA
Consider liver biopsy
Yes
Consider ERCP
387
GGT or liver
fraction elevated
phosphatase (ALP) level in

a well patient. AMA,
antimitochondrial antibody;
ERCP, endoscopic retrograde cholangiopancreatography; GGT, -glutamyltransferase. (Modified
from Kamath PS. Clinical
approach to the patient with
abnormal liver tests. Mayo
Clin Proc. 1996;71:108995. By permission of Mayo
Foundation for Medical
Education and Research.)
PULMONARY ARTERY CATHETER
DESCRIPTION
Pulmonary artery catheter (PAC) is a 110-cm, 7F, heparinbonded, polyvinylchloride, balloon-tipped, flow-directed
catheter inserted through the central venous system into the
pulmonary circulation (Fig. 1).
The balloon is 1-2 cm from the tip and inflated by 0.8-1.5 mL
of air, allowing for flotation during insertion.
The catheter shaft is marked with black bands at 10-cm increments, which aid in determining location of the catheter tip
within the central circulation.
A thermistor wire that ends 4-6 cm proximal to the catheter
tip provides for
Cardiac output calculations (via thermodilution technique)
Intermittent measurements of pulmonary artery occlusion
pressure (PAOP)
Continuous measurements of central venous pressure and
pulmonary artery pressures
Features That Differ By Model and Manufacturer
Number of lumens (2-5)The fifth lumen allows administration of fluids or medications.
Temporary cardiac pacingatrial, ventricular, or atrioventricular sequential
Measurements of oxygen saturation
Continuous determination of right ventricular ejection fraction
A proximal port 10 cm from the catheter tip measures pressure
changes from the right ventricle to the pulmonary artery,
helping detect distal migration of the catheter tip (Fig. 2).
Special abbreviations used in this chapter: PAC, pulmonary artery catheter; PAD,
pulmonary artery diastolic [pressure]; PAOP, pulmonary artery occlusion pressure.
389
390
Proximal
(right atrial)
opening
Thermistor
opening
C. Proximal
port
A. Distal
port
B. Balloon
inflation port
D. Thermistor
connector
Distal
opening
Fig. 1. The quadruple-lumen pulmonary

artery catheter. (From Darovic GO.
Pulmonary artery pressure monitoring.
In: Darovic GO, Franklin CM, editors.
Handbook of hemodynamic monitoring.
Philadelphia: WB Saunders Company;
1999. p. 121-57. Used with permission.)
20
RA
RV
PA
PCWP
0
20
10
0
Fig. 2. Typical waveforms during insertion of a pulmonary artery catheter. Right atrium (RA), right ventri-
391
cle (RV), pulmonary artery (PA), and pulmonary capillary wedge pressure (PCWP) tracings are shown. Note
the increase in diastolic pressure upon entering PA. (From Preas HL II, Suffredini AF. Pulmonary artery
catheterization: insertion and quality control. In: Tobin MJ, editor. Principles and practice of intensive care
monitoring. New York: McGraw-Hill; 1998. p. 773-95. Used with permission.)
mm Hg
10
INDICATIONS
Insert PAC only if the answer to both questions below is yes.
Will the information obtained likely change current
management?
Is expertise available for optimal placement, data collection, and maintenance of the catheter?
Accepted Diagnostic and Therapeutic Indications
Shock
Diagnosis
Differentiate between different types of shock
Treatment
Assess intravascular volume status
Guide fluid and pressor therapy
Optimize oxygen delivery (controversial)
Pulmonary edema (cardiogenic and noncardiogenic)
Diagnosis
Confirm cause
Treatment
Titrate left ventricular preload (cardiac failure)
Assess and titrate intravascular volume (renal failure)
Diagnosis of pulmonary lymphangitic carcinomatosis
(wedged catheter cytology)
Diagnosis
Assessment of severity of left-to-right shunting in setting of ventricular septal defect
Treatment
Right ventricular infarction with hypotension
Intraoperative monitoring (high-risk surgery)
CATHETER INSERTION
Complete, sterile barrier precautions should be used when
inserting a PACsterile mask, gown, gloves, towels, and a
full-length sheet covering the patient.
Internal jugular and subclavian veins are the sites of choice.
Femoral vein is the least desirable site because of increased
incidence of intravascular catheter infections.
Common insertion sites and their distances to the right atrium, right ventricle, pulmonary artery, and wedge position are
listed in Table 1.
392
General Dos and Donts
Dos
Always have at least one more person in the room.
Continuously assess the patient for signs of distress.
Inflate the balloon to the manufacturers recommended volume (know this ahead of time!).
Advance the catheter with the balloon inflated.
Check for distal migration of the catheter tip (balloon inflation volume is suddenly much less than recommended by
manufacturer).
Inflate the balloon slowly and stop at any point a sudden
increase in resistance is felt (overwedged) or if no resistance is felt (balloon rupture).
Insert under continuous ECG monitoring with a defibrillator
at the bedside.
Minimize balloon inflation time/cycles.
Check a chest X-ray after positioning the PAC.
Donts
Never withdraw the catheter with the balloon inflated
(increases risk for intracardiac trauma, e.g., valve rupture).
Table 1. Insertion Sites and Distances*

Vein
Right internal
jugular
Left internal
jugular
Subclavian
Femoral
Right antecubital
Left antecubital
Right
atrium
Right
ventricle
Pulmonary
artery
Wedge
position
10-15
25
40
45
15-20
30
45
50
10
40-50
30-40
20
65
60
35
80
75
40
85
80
35-45
65
80
85
*All distances are in centimeters.

Modified from Darovic GO. Pulmonary artery pressure monitoring. In:
Darovic GO, Franklin CM, editors. Handbook of hemodynamic monitoring.
Philadelphia: WB Saunders Company; 1999. p. 121-57. Used with permission.
393
Do not forcefully pull on a catheter that does not withdraw

easily.
Do not use fluids to inflate the balloon.
Do not manipulate the catheter frequently (increases risk of
infection).
Do not exceed the recommended inflation volume.
Do not keep the catheter in place for prolonged periods.
Waveforms
The typical waveforms obtained during passage of the PAC
through the right atrium (central venous pressure), right ventricle, and pulmonary artery are shown in Figure 2.
Entrance into the pulmonary artery is marked by the appearance of a dicrotic notch.
A typical PAOP tracing is illustrated in Figure 3. Note the
rise and fall in baseline pressure associated with respiratory
variation.
Depending on whether the patient is breathing spontaneously or is given positive pressure ventilation, PAOP is
determined by appropriate measurement of the pressure in
relation to the baseline.
With positive pressure ventilation, measure PAOP at
end-expiration (arrows in Fig. 3).
With spontaneously breathing patients, PAOP is also
measured at end-expiration (arrowhead), but the inflection point differs from that measured with positivepressure ventilation because of the generation of negative intrathoracic pressure.
LIMITATIONS
Controversy surrounds pulmonary artery catheterization.
No study has shown an increase in survival in catheterized
patients; in fact, the observational study of Connors et al.
(JAMA. 1996;276:889-97) demonstrated an increased mortality rate. This result is believed to be due to catheter complications, data misinterpretation, and aggressive care.
Accurate interpretation of data from a PAC is based on the
assumption that a continuous, unbroken column of fluid
(blood) extends from the left ventricle to the catheter tip.
Any perturbation that interferes with this column of fluid
will affect data accuracy.
394
Pulmonary artery pressure

Pulmonary artery occlusion pressure
8
0
14:39:31
14:39:35
14:39:39
Time
Fig. 3. Typical pulmonary artery pressure tracing (including wedge procedure) during positive pressure mechanical ventilation.
Arrows, recordings at end expiration. Arrowhead, timing of peak pressure administered by the ventilator.
395
mm Hg
16
Various anatomic, physiologic, and extrinsic conditions can

affect the accuracy of data:
Severe mitral regurgitation
Severe tricuspid regurgitation
Mitral stenosis/left atrial myxoma
Left ventricular dysfunction (PAOP is a reflection of left
ventricular end-diastolic volume [preload]). A noncompliant ventricle will affect the accuracy of data obtained
(e.g., ventricular hypertrophy, myocardial ischemia).
Catheter whip (e.g., hyperdynamic circulation, excessive
catheter length in the right ventricle, catheter tip located
near the pulmonic valve)
Miscellaneous (positive pressure ventilation, location of
catheter tip in lung zones 1 or 2)
CONTRAINDICATIONS
Relative
Coagulopathy
Permanent pacemaker recently implanted
Left bundle branch block
Bioprosthetic tricuspid (or pulmonic) valve
Absolute
Right-sided endocarditis
Mechanical tricuspid (or pulmonic) valve
Presence of thrombus or tumor in a right chamber of the
heart
TROUBLESHOOTING
Despite proper insertion technique, it may not be possible to
obtain a good waveform. Here are some of the possible causes and solutions.
Absence of Pulmonary Artery Waveform Pattern
Thrombus formation on catheter tip, inability to aspirate
blood from the distal port: Replace the catheter.
Leak in the system: Tighten loose connections.
Defective transducer: Replace the transducer. If air is suspected in the transducer, purge air.
Loose cable or electrical connections: Tighten loose
connections.
396
Unable to Obtain PAOP Measurement
Retrograde movement of the catheter tip into the pulmonary
artery: Inflate the balloon and reposition the catheter tip
into the wedge position.
Balloon rupture (see COMPLICATIONS)
Pulmonary Artery Waveform is Damped
Catheter tip is lodged against vessel wall: Ask patient to
cough or move side-to-side. Also, try gentle aspiration, followed by flushing.
Thrombus formation on catheter tip (see above, Absence of
Pulmonary Artery Waveform Pattern)
Air trapped in tubing: Aspirate air from the system.
Distal migration of catheter tip into wedged position resulting
in a PAOP waveform: Withdraw the catheter until a PAOP
tracing is obtained with the recommended inflation volume.
Sudden Changes in Pressure Measurements or Pressure

Measurements Inappropriate to the Patients Condition
Change in the patients position: Transducer must be leveled
to the patients right atrium.
Inaccurate zero referencing: Reset transducer to zero
atmosphere.
HEMODYNAMIC VARIABLES
Normal values for hemodynamic variables used in critical
care medicine are given in Table 2.
CLINICAL SCENARIOS
Examples of common hemodynamic variables are given in
Table 3.
Four principles should guide PAC use and therapy at all times:
Adequate placement and maintenance
Proper data collection
Proper interpretation of hemodynamic data
Appropriate alteration of therapy based on acquired data
When data obtained by the PAC are no longer being used to
actively guide or alter therapy, the catheter should be removed.
397
Table 2. Normal Hemodynamic Variables

Variable
Right atrium (CVP)
Right ventricle
Pulmonary artery
Mean pulmonary artery pressure
MAP
PAOP
CI
SVRI
PVRI
SVI
RVEF
Unit
Range
mm Hg
mm Hg
mm Hg
mm Hg
mm Hg
mm Hg
L/min per m2
dyne.sec.cm-5
0-8
25/0-6
15-30/6-12*
9-16
70-105
6-12
2.8-4.2
1,600-2,400
dyne.sec.cm-5
mL/beat per m2
69-177
30-65
0.40-0.60
CI, cardiac index; CVP, central venous pressure; MAP, mean arterial pressure; PAOP, pulmonary artery occlusion pressure; PVRI, pulmonary vascular
resistance index; RVEF, right ventricular ejection fraction; SVI, stroke volume index; SVRI, systemic vascular resistance index.
*Systolic/diastolic.
COMPLICATIONS
Before, during, and after insertion, beware of complications!
Immediate Complications
Pneumothorax
Suspected when
Air is withdrawn into the venous access needle during
initial puncture
Patient experiences increased dyspnea or hemodynamic
compromise after central access
Chest tube should be placed depending on extent of pneumothorax and patients clinical picture.
This is why bilateral attempts at central venous access
should never be performed unless a chest X-ray shows
the absence of pneumothorax.
Atrial or ventricular dysrhythmiasgenerally benign
Most likely to occur during passage of the PAC through the
right ventricle during flotation or catheter pullback
Further advancement of the PAC terminates dysrhythmias.
Air embolismusually occurs during insertion of the catheter
Trendelenberg position reduces the risk.
398
Table 3. Hemodynamic Variables of Common Clinical Scenarios*

R ventricle,
mm Hg
Pulmonary
artery,
mm Hg
PAOP,
mm Hg
Cardiac
index,
L/min/m2
SVR
dynes/
s/cm-5
PVR
dynes/
s/cm-5
0-2
6
15-20/0-2
45-0/6-8
15-20/2-6
45-50/30-35
2-6
30-35
<2.0
<2.0
>1,500
>1,500
250
250
0-2
0-4
8-12
12-18
>6
0-6
6
12-20
20-25/0-2
25/4-10
50/12
25/12-18
80/>6
80-100/0-6
60/6-8
30/12-20
20-25/0-6
25/4-10
50/12-15
25/12-18
80/35
80-100/40
60/35
30/12
0-6
4-10
12
12-18
<12
<12
30
<12
2.5
<2.0
<2.0
<2.0
~2.0
<2.0
<2.0
<2.0
<1,500
>1,500
>1,500
>1,500
>1,500
>1,500
>1,500
>1,500
<250
>250
>350
250
>350
>350
>250
>250
0-6
30-40/0-6
30-40/18-25
>18
>2.0
>1,500
>250
0-6
25/0-6
25/12-18
18
2.5
1,500
250
399
L, left; PAOP, pulmonary artery occlusion pressure; PVR, pulmonary vascular resistance; R, right; SVR, systemic vascular resistance.
*The three most critical data points for each scenario are in bold.
Hypovolemic shock
Cardiogenic shock
Distributive shock
Early
Late
Acute pulmonary embolism
Cardiac tamponade
Cor pulmonale
Ventricular septal rupture
Acute R ventricle infarction
with failure
Acute L ventricle infarction
with failure
Acute L ventricle infarction
without failure
R atrium,
mm Hg
Increased riskhypovolemia with low filling pressures

or development of highly negative intrathoracic pressures
during inspiration.
If suspected, place patient left side down. Small amounts
of air are tolerated if confined to the pulmonary circulation,
but severe respiratory distress can occur.
Catheter knottingmore apt to occur in the presence of a
dilated right ventricle.
Interventional radiology and surgery are options for
deknotting.
Do not attempt to pull PAC back if there is resistance!
Delayed Complications
Balloon rupturecan be immediate
Risks include multiple inflations, prolonged indwelling
time, exceeding recommended inflation volume.
Possibility of fragment or air emboli
If the PAC is needed, you may still keep it in, and if pulmonary artery diastolic (PAD) pressure correlates with
PAOP, PAD pressure may be used to monitor filling of
left side of the heart.
Pulmonary artery perforationcaused by overinflation of
the catheter with or without distal migration
Risk factors include multiple manipulations, exceeding
recommended inflation volume, distal migration of the
stiff catheter tip, pulmonary hypertension, severe mitral
regurgitation, advanced age, female, anticoagulation.
Usually presents as hemoptysis, often massive
Call surgery immediately!
Intubate the mainstem bronchus of the uninvolved lung
if massive bleeding occurs.
Place the affected side in the dependent position.
Positive end-expiratory pressure and proximal positioning
of the catheter can be attempted as temporizing measures
while waiting for surgery.
Thromboembolic phenomenon
Often clinically silent, but can present as damped waveforms, poor IV fluid infusion or increased pulmonary artery
systolic/diastolic pressure with a widened PAD pressureto-PAOP gradient (suggestive of pulmonary embolism)
Remove and, if indicated, replace the catheter.
400
Infection
Risk increases after 72-96 hours.
There is poor correlation between blood cultures and
catheter infection.
If suspected, remove the catheter.
If another catheter is needed, obtain a new site (do not
exchange the catheter over a guidewire).
STEPWISE APPROACH TO PLACEMENT OF A PAC

Position the patient supine, and position yourself comfortably.
Clean the skin with an iodine solution, and drape the area and
patient with sterile towels and full-length sheet (the more
the better).
Anesthetize the skin with 1% lidocaine.
Locate the internal jugular vein with a 21-gauge, 1.5-inch
needle attached to a 5-mL syringe. Once the free flowing
blood is aspirated, detach the syringe, leaving the locator
needle in place. (This step is not needed for the subclavian
or femoral vein.)
Insert an 18-gauge guidewire introducer needle attached to
a 5-mL syringe next to the locator needle, aspirating until
the free flow of blood is noted. Then, remove the locator
needle.
Detach the syringe from the 18-gauge guidewire introducer
needle. Generally, blood will flow freely from the needle
hub (a tip that you are still in the right place).
Thread the guidewire (soft, J-end first) through the
guidewire introducer needle.
Holding the guidewire in place, withdraw the guidewire
introducer needle.
With a scalpel blade, make a small incision to enlarge the
puncture site.
Insert the vessel dilator through the introducer (they become
a unit).
Advance, twisting the vessel dilator-introducer unit over the
guidewire.
Remove the guidewire and vessel dilator, leaving the introducer in place.
401
Aspirate the introducer and the attached sideport to confirm

intravascular placement, then flush.
Secure in place with sutures.
Prepare the PAC.
Wipe the external surface with gauze soaked in sterile saline,
and flush the proximal and distal catheter lumens to remove
air that may gain access to the circulation.
Check balloon integrity by submerging the catheter tip in
sterile water, inflating the balloon, and checking for air leaks.
Deflate the balloon and insert the PAC through the sterile
sleeve, and pull the sleeve toward you to keep it out of the way.
With the help of a nonsterile assistant, connect flush-line
catheters to the appropriate ports of the PAC (via transducers, providing PAC distal port pressure tracing monitoring
during subsequent advancing of the catheter, while preventing air intravasation via any open ports).
Advance the distal tip of the PAC approximately 10-15 cm.
At this point, the waveform typical of the central venous circulation-right atrium will be noted. Further advancement
is guided by the observed waveforms (see Fig. 2 while doing
this). Attach the sterile sleeve to the introducer hub.
402
PULMONARY FUNCTION TESTS
DEFINITIONS AND NORMAL VALUES

Most results of pulmonary function tests are reported as a percentage of predicted (the most important exception is
FEV1:FVC ratio).
Normal ranges for many tests vary with age and/or size.
Rule of thumb normal values (for quick checks before a
final report) are given below.
FVC (forced vital capacity): measure of usable lung
capacity (volume)
Normal is >80% of predicted.
FEV1 (forced expiratory volume in 1 second): rate of
expiration = degree of obstruction
Normal is >80% of predicted but varies with age and
size.
FEV1/FVC ratio: the presence or absence of obstruction.
0.7 is an acceptable rule of thumb (>0.7 = normal); it
varies with age.
Provocation (methacholine) challenge
Inhalation of a substance such as methacholine induces
bronchospasm in susceptible patients (asthma).
Decrease in FEV1 by >20% is positive (but is found
in 10% of normals).
Bronchodilator response
FVC and FEV1 measured before and after a bronchodilator
Special abbreviations used in this chapter: ABG, arterial blood gas; DLCO,
diffusing capacity of carbon monoxide; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; MEP, maximal expiratory pressure; MIP, maximal inspiratory pressure; MVV, maximal voluntary ventilation; TLC, total lung
capacity.
403
Improvement of 12% and 200 mL indicate significant

reversibility.
DLCO (diffusing capacity of carbon monoxide)
It measures how much carbon monoxide is absorbed
in a single breath.
Result depends on alveolar membrane, blood flow, and
hemoglobin.
Lower limit for adults (>20 years old): male = predicted 8; female = predicted 6.5 (about 75%-80%)
Lung volumes
TLC (total lung capacity): measure of total lung volume
(FVC + residual volume)
Residual volume: volume of gas remaining in lung
after complete exhalation
Flow loops
Inspiratory flow loops are used to evaluate extrathoracic (above thoracic inlet) obstruction.
Expiratory flow loops are used to evaluate intrathoracic obstruction (asthma, COPD, trachea below thoracic
inlet).
MIP (maximal inspiratory pressure) and MEP (maximal
expiratory pressure)
Measure peak pressure that can be generated with inspiratory and expiratory effort
MVV (maximal voluntary ventilation)
Tests both airflow and muscle strength
Normal is FEV1 40 (lower limit is FEV1 30).
ABGs (arterial blood gases) can be ordered in conjunction
with pulmonary function tests.
Can be obtained before and during exercise if desired
(requires arterial catheter or multiple arterial punctures)
INDICATIONS
Spirometry
Includes FVC, FEV , and sometimes MVV or bronchodilator
1
testing
Can be done at bedside
Most cost-effective pulmonary function test.
Indications
Straightforward diagnostic problem (asthma, uncomplicated COPD)
404
Screening asymptomatic smoker (15%-25% will have

abnormal results)
Initial evaluation of most pulmonary symptoms (along
with chest X-ray)
Logistic issues (patient unable to travel for complete
exam)
Often adequate for monitoring disease
Annual certification for use of respiratory protection
equipment
Complete Pulmonary Function Testing

Usually includes spirometry before and after bronchodilator,
lung volumes, and DLCO.
Indications
Complex respiratory symptoms or disease
Distinguish between asthma and COPD
DLCO is decreased in emphysema.
Distinguish between obstructive and restrictive diseases
Distinguish between parenchymal and extraparenchymal
restriction
Note: even when complete pulmonary function testing
is performed initially, limited studies are often adequate for
follow-up.
DLCO
Indications
Restrictive lung disease (very sensitive to progression)
Obstructive lung disease (abnormal in emphysema)
Vascular disease (chronic pulmonary embolism, pulmonary
hypertension [not sensitive])
Before and during treatment with a medication toxic to
lung (amiodarone, bleomycin)
Methacholine Challenge
Indications
Confirm suspicion of reactive airway disease
Chronic unexplained cough (cough variant asthma)
Evaluate response of asthma to treatment
405
Lung Volumes
Indications
Low FVC
Interstitial/restrictive lung disease
Neuromuscular weakness
Obesity
Inspiratory Loops
Indication
Suspicion of upper airway obstruction
MIP/MEP
Indication
Suspicion of neuromuscular disease
ABGs
Indications
Before and during exercise may detect subtle abnormalities
Severe COPD (staging, need for or response to oxygen
therapy, surgical risk)
Severe chest wall or neuromuscular restriction (e.g., severe
scoliosis, amyotrophic lateral sclerosis, Guillain-Barr
syndrome)
INTERPRETATION
General Approach to Pulmonary Function Tests
Examine FEV /FVC ratio and shape of the curve.
1
Low FEV 1 /FVC or scooped out (concave) curve =
obstruction
Next step, examine FEV 1 to quantitate degree of
obstruction.
60%-80% = mild obstruction
40%-60% = moderate obstruction
<40% = severe obstruction
Next, check bronchodilator response.
Significant reversibility if FEV1 or FVC improve by
both 200 mL and 12%
Check DLCO.
Low = emphysema, otherwise asthma or chronic
bronchitis
406
Examine TLC (or FVC if TLC is not available).

Low = restrictive disease (parenchyma, chest wall, or neuromuscular)
Curve = small; witchs hat
Next step, check TLC if not already done.
If TLC is low, check DLCO.
Low DLCO = parenchymal lung disease (e.g., interstitial lung disease)
Disproportionately high residual volume (high residual volume/TLC) and normal DLCO, consider neuromuscular disease.
Normal DLCO and residual volume = chest wall
deformity/limitation (e.g., kyphosis, obesity, weakness)
FVC used for quantitation
60%-80% = mild restriction
50%-60% = moderate restriction
<50% = severe restriction
Check DLCO
Normal, with abnormal spirometry
Asthma
Chronic bronchitis
Chest wall deformity
Low
Normal spirometry
Anemia (7% decrease in D LCO for each 1 g/dL
decrease in hemoglobin)
Pulmonary embolism
Obliterative vascular disease (e.g., scleroderma, systemic lupus erythematosus)
Abnormal spirometry
Emphysema
Parenchymal restrictive disease
Pulmonary edema
407
Decreased lung volume (pneumonectomy)

Quantitation
65%-normal = mild (recall that normal range
varies)
50%-65% = moderate
<50% = severe
High (spirometry usually normal)
Obesity
Asthma
Exercise (nonresting state)
Polycythemia
Left-to-right shunt
Pulmonary hemorrhage
Check MVV
Low MVV with otherwise normal spirometry suggests
Inspiratory (extrathoracic) obstruction
Poor performance
Other tests
Methacholine challengeif considering asthma
Positive if >20% decrease in FEV1
MIP/MEPif considering neuromuscular weakness
Low MIP and normal MEP suggest diaphragmatic
weakness.
Low MEP and normal MIP suggest spinal cord injury
below C4.
Both low MEP and MIP suggest muscle weakness or
poor performance
ADDITIONAL TESTING
Chest X-rayif not already done, get one.
Restrictive Parenchymal Lung Disease

CBC, rheumatoid factor, antinuclear antibodies, cryoglobulins, ABGs
Usually proceed with high-resolution CT of chest
Consider lung biopsy in appropriate setting.
Isolated Low DLCO

CBC (calculate correction as above if anemic), rheumatoid
factor, antinuclear antibodies, ABGs
408
Consider ventilation-perfusion scan or contrast chest CT

(acute or chronic pulmonary embolism)
Echocardiography (evaluate for pulmonary hypertension)
Neuromuscular Weakness
Careful physical exam
CBC, electrolytes (potassium, calcium, magnesium, phosphate), ABGs, CK, serum protein electrophoresis
EMG is crucial.
Consider acetylcholine receptor-binding antibodies (myasthenia gravis?).
409
THYROID FUNCTION TESTS
Lisa S. Chow, M.D.
Rebecca S. Bahn, M.D.
PRINCIPLES
Need to correlate thyroid function test results with clinical suspicion and physical exam findings
Symptoms and signs suggestive of hyperthyroidism
Symptomsheat intolerance, increased sweating, weight
loss, increased appetite, anxiety, palpitations, fatigue
Signstachycardia (especially new-onset atrial fibrillation), hyperkinetic movements, tremor, abnormal thyroid
exam, exophthalmos
Symptoms and signs suggestive of hypothyroidism
Symptomscold intolerance, decreased sweating, slow
movements, weight gain, constipation, hoarseness,
paresthesias
Signsbradycardia; delayed relaxation of reflexes; dry,
coarse, cool skin; periorbital puffiness
Prevalence of thyroid disease~0.6% in the population
(hypothyroidism/hyperthyroidism ratio is 1:1)
Comorbid acute illness often leads to inaccurate values. If
thyroid dysfunction is suspected, repeat tests after acute
illness resolves.
Thyroid-stimulating hormone (TSH) level is the initial test
for evaluating thyroid function.
If TSH is abnormal, the next test should be a free thyroxine
(T4) level. Free T4 index is another option.
In inpatient setting, drugs (especially iodine in contrast dye)
frequently cause abnormal thyroid function tests.
Normal values for thyroid function tests are listed in Table 1.
Special abbreviations used in this chapter: T4, thyroxine; TSH, thyroid-stimulating hormone.
411
Table 1. Normal Values (Mayo Clinic Laboratory)

for Thyroid Function Tests
Test
TSH
Total T4
Free T4
Total T3
Free T3
Thyroid
autoantibodies
TSI
Comment
Test of choice
Direct measurement of
bound & free T4
Measurement of functional (free) T4
Used only in hyperthyroidism evaluation
Rarely used
Positive in Hashimoto
disease
Positive in Graves
disease
Thyroglobu- Used to follow-up
lin
thyroid cancer
Normal value
0.3-5.0 mIU/L
5.0-12.5 g/dL
0.7-2.0 ng/dL
80-180 ng/dL
2.3-4.2 pg/mL
Thyroglobulin antibody
titer, <1:100
Microsomal antibody titer,
<1:100
1.3 (index value, no unit
used)
Depends on circumstances
T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; TSI,

thyroid-stimulating immunoglobulin.
INDICATIONS
Indications for thyroid function tests are listed in Table 2.
An algorithm for evaluating high or low levels of TSH is
given in Figure 1.
FURTHER EVALUATION
Hyperthyroidism
Radioiodine uptake with or without scan
Thyroid nodule
Fine-needle aspiration biopsy of palpated nodule
Hypothyroidism
Antithyroid antibodies
If positive, consider Hashimoto thyroiditis.
If negative, consider a non-Hashimoto cause.
Subclinical hypothyroidism
Repeat thyroid function tests in 6 months.
Sick euthyroid
Repeat thyroid function tests after acute illness resolves.
412
Indication
Evaluation of a healthy patient
(i.e., seen in clinic)
Evaluation of a sick patient
(i.e., seen in hospital)
Test
TSH
Free T4
TSH
Free T4
T4, thyroxine; TSH, thyroid-stimulating hormone.
Sensitivity, %
Hyperthyroid
Hypothyroid
>99
95
99
95
99
90
99
60
Specificity, %
Hyperthyroid
Hypothyroid
>99
95
95
97
99
90
95
80
413
Table 2. Indications for Thyroid Function Tests and the Corresponding Sensitivity and Specificity
414
TSH
Low
High
Normal
Free T4
Needs further work-up (imaging

& other pituitary tests) if CNS
disease in differential diagnosis
Normal
High
Low
(0.1-0.3 mIU/L)
Suppressed
(<0.1 mIU/L)
Free T4
High
Low
Subclinical hypothyroidism
Insufficient T4 replacement
Thyroid
autoantibodies
TSH-secreting tumor
Peripheral resistance to
thyroid hormone
Hashimoto
thyroiditis
Severe illness
Drug effects
(iodine, lithium, thioureas)
Idiopathic hypothyroidism
Normal
Central hypothyroidism
Concurrent severe illness
131
T3
High
High
T3 toxicosis
Plummer disease
Toxic adenoma
I131 Uptake
Low
Exogenous T3
Normal/low
Uptake
Low
Thyroiditis (de Quervain)
Concurrent severe illness
Exogenous T4
Drug effects (especially iodine)
High
Graves disease
Plummer disease
Toxic adenoma
Drug effects (somatostatin, dopamine, steroids)

Subclinical hyperthyroidism
Recovery from hyperthyroidism
Concurrent nonthyroidal illness
Fig. 1. Algorithm for evaluating high or low levels of thyroid-stimulating hormone (TSH). CNS, central nervous system; T3, triiodothyronine; T4, thyroxine.
CAVEAT
Because of their many comorbid conditions, hospitalized
patients often have thyroid function test abnormalities for
reasons other than thyroid disease.
If the diagnosis of thyroid disease is unclear, it is critical to
repeat thyroid function tests after hospital discharge.
415
III DISEASES
ACID-BASE DISORDERS
Javier D. Finkielman, M.D.
DEFINITION
Normal arterial blood pH is 7.40 or [H+] = 40 ([HCO ] = 24).
3
Under normal conditions, the net amount of acid secreted
and the consequent renal production of bicarbonate equals the
rate of proton generation, preserving the [H+] balance.
Failure to maintain the proton or bicarbonate concentration
leads to acidosis or alkalosis.
When the disorder involves only one process, the result is a
simple acid-base disorder; when more than one process, it is
a mixed acid-base disorder.
CLASSIFICATION
Simple Acid-Base Disturbances
Metabolic Acidosis
pH <7.37 acidosis
Low [HCO ] metabolic
3
Normal compensation low PCO
2
Expected Range of Compensation
PCO = 1.5 [HCO ] + 8 2
2
3
PCO = last 2 digits of the pH
2
Anion Gap
Normal anion gap = 12 2
Anion gap = [Na+] ([Cl] + [HCO ])
3
High anion gap metabolic acidosis with increased anion gap
Metabolic Alkalosis
pH >7.43 alkalosis
Special abbreviation used in this chapter: RTA, renal tubular acidosis.
417
High [HCO3] metabolic

Normal compensation high PCO2

PCO = 40 + 0.6 [HCO ]
2
3
PCO = 0.9 [HCO ] + 9
2
3
Respiratory Acidosis
pH <7.37 acidosis
High PCO respiratory
2
Normal compensation high [HCO ]
3
Acute
[HCO3] = 0.1 (PCO2)
Chronic
[HCO3] = 0.4 (PCO2)
Respiratory Alkalosis
pH >7.43 alkalosis
Low PCO respiratory
2
Normal compensation low [HCO ]
3

Acute
[HCO3] = 0.2 (PCO2)
Chronic
[HCO3] = 0.5 (PCO2)
Mixed Acid-Base Disturbances
When two or more acid-base conditions are present simultaneously, the patient has a mixed disorder.
Any combination may occur except for respiratory alkalosis
and acidosis, because one can never concurrently overexcrete and underexcrete carbon dioxide.
To diagnose mixed disorders
Know how the simple disorders affect pH, P CO2, and
bicarbonate
Know the extent of the compensatory mechanism that
ought to occur for any given degree of primary disorder
If the compensatory change does not fit one of the formulas
418
III DISEASES
or the yellow areas in Figure 1, a mixed acid-base disorder

is present.
For example, in metabolic acidosis the primary disturbance
is bicarbonate lost and the compensatory response is increased
ventilation, which reduces the PCO2. If the PCO2 is lower
than expected based on the compensatory mechanism, respiratory alkalosis is present. If the PCO2 is higher than
expected, respiratory acidosis is present (Table 1).
In addition, if the anion gap is high, regardless of the pH
and the primary acid-base disorder, a component of metabolic
acidosis with high anion gap is present.
Arterial blood [H+], nmol/L
100
90
80
70
60
50
40
30
20
60
120 110 100 90
80
70
60
50
40
56
Arterial plasma [HCO3 ], mmol/L
52
35
48
44
Metabolic
alkalosis
Chronic
respiratory
acidosis
40
30
25
36
32
20
28
Normal
24
Acute
respiratory
alkalosis
Acute
respiratory
acidosis
20
16
15
10
12
Chronic
respiratory
alkalosis
Metabolic
acidosis
PCO2 (mm Hg)
4
0
7.0
7.1
7.2
7.3
7.4
7.5
7.6
7.7
7.8
Arterial blood, pH
Fig. 1. Acid-base nomogram. (From DuBose TD Jr, Cogan MG,

Rector FC Jr. Acid-base disorders. In: Brenner BM, editor. The kidney. 5th ed. Philadelphia: WB Saunders Company; 1996. p. 929-98.
419
420
Table 1. Summary of Simple and Mixed Acid-Base Disorders

Disorder
Initial change
Compensation
Degree of compensation
Metabolic acidosis
HCO3 decrease
PCO2 decrease
Metabolic alkalosis
HCO3 increase
PCO2 increase
Respiratory acidosis
PCO2 increase
HCO3 increase
Respiratory alkalosis
PCO2 decrease
HCO3 decrease
Lower
Higher
Lower
Higher
Lower
Higher
Lower
Higher
Second disorder
Metabolic acidosis
Metabolic alkalosis
Metabolic acidosis
Metabolic alkalosis
Modified from Narins RG, Emmett M. Simple and mixed acid-base disorders: a practical approach. Medicine (Baltimore). 1980;59:161-87. Used with
permission,
III DISEASES
In anion gap metabolic acidosis, it is helpful to compare the

[HCO3] with the anion gap. The illustrated concept of the anion gap reflects any increase in the anion
gap above normal should lead to ~1:1 titration of 1 mEq of
bicarbonate.
For example, an anion gap of 20 reflects an excess anion
gap of 8 (20 12 = 8). Therefore, the expected decrease
in serum bicarbonate should be 8, or a serum bicarbonate
level of 16 (24 8 = 16).
If the [HCO3] > anion gap, a combination of anion
gap and nonanion gap metabolic acidosis is present.
If the [HCO3] < anion gap, a combination of anion
gap metabolic acidosis and metabolic alkalosis is present.
METABOLIC ACIDOSIS
In metabolic acidosis, bicarbonate is lost or nonvolatile acid
is gained. Metabolic acidosis does not necessarily mean an
abnormal pH because respiratory compensation or the combination with a second acid-base disorder could result in
near-normal or normal pH, respectively.
Metabolic Acidosis With Increased Anion Gap

Causes
Causes are listed in Table 2.
Management
Diabetic Ketoacidosis
Volume replacement (not in end-stage renal disease) and
insulin form the cornerstone of treatment.
IV insulin bolus (0.1 U/kg) is followed by a continuous infusion of insulin (starting dose 0.1 U/kg per hour).
1L of isotonic saline or Ringer lactate should be given rapidly
IV on arrival in the first hour, then 0.5-1 L of half normal
saline in the second and third hours.
From the fourth hour, the amount of fluid should be estimated
based on urine output and clinical assessment.
Glucose level should be determined hourly, and when it falls
around 200-300 mg/dL, 5% glucose solutions should be added.
421
Table 2. Causes of Metabolic Acidosis With Increased

Anion Gap
Endogenous
Ketoacidosis
Diabetes mellitus
Starvation
Alcohol-induced
Lactic acidosis
Hypoxic (type A)
Nonhypoxic (type B)
Uremia
Exogenous
Methanol
Ethylene glycol
Salicylate
Paraldehyde
From Laski ME, Kurtzman NA. Acid-base disorders in medicine. Dis Mon.
1996;42:90-125. Used with permission.
Henceforth, insulin infusion and glucose infusion should be

adjusted so glucose level remains around 250 mg/dL.
Potassium replacement is usually needed; if the admission
value is normal or low, potassium should be given early.
Electrolytes should be checked every 3-4 hours.
Bicarbonate should be considered if pH <7.00, and phosphate should be considered if <1 mg/dL.
Insulin infusion should be switched to SQ dosage after ketoacidosis has resolved (anion gap and bicarbonate have normalized).
Lactic Acidosis
Lactic acidosis occurs when oxygen delivery to the cells is
inadequate (type A) or the cell is unable to use oxygen.
Type A results from systemic (shock, carbon monoxide
poisoning) or localized (interruption of regional vasculature,
mesenteric ischemia, acute arterial thrombosis) tissue
hypoxia.
Type B is the consequence of drugs, toxins, and organ failure
(phenformin, metformin, cyanide intoxication, zidovudine,
didanosine, zalcitabine, methanol, some hematologic malignancies, liver failure, severe acute pancreatitis).
The diagnosis is usually one of exclusion and lactate can be
measured.
422
III DISEASES
Treatment consists of restoration of tissue perfusion and

oxygenation.
Intoxications
Methanol and ethylene glycol are metabolized to glycolate
or formate.
An indication of increased alcohol levels is an increase in
the osmolar gap: the difference between measured and calculated serum osmolality.
The calculated (calc) serum osmolality is calculated as follows:
Osmolality(calc) = 2 [Na+] + [glucose]/18 +
[BUN]/2.8 + [ethanol]/4.6
Na is in mEq/L and BUN, glucose, and ethanol in mg/dL
(ethanol could be excluded).
If this difference is >15-20, the presence of toxic alcohol
is likely.
Treatment requires infusion of ethanol to produce a serum
level of 100-200 mg/dL, followed by hemodialysis, or the use
of fomepizole, an alcohol dehydrogenase inhibitor.
Aspirin can produce respiratory alkalosis, mixed respiratory alkalosis and metabolic acidosis, or (less commonly) pure
metabolic acidosis.
Treatment consists of limiting further drug absorption
with activated charcoal, urine alkalization, and establishing a high urinary flow rate. Hemodialysis should be considered for patients with renal failure or for severe cases.
Metabolic Acidosis With Normal Anion Gap

Causes
Diagnosis
Urinary anion gap may help to distinguish gastrointestinal
from renal loss of bicarbonate as the cause of hyperchloremic
metabolic acidosis.
Urinary anion gap = [Nau+ + Ku+] [Clu]
A negative urinary anion gap results from a nonrenal cause
of hyperchloremic acidosis (e.g., diarrhea).
423
Urinary anion gap is positive in renal tubular acidosis

(RTA).
Management
Nonrenal
Diarrhea is the most common cause of hyperchloremic metabolic acidosis. If renal function is normal, therapy should
focus on resolving excessive enteric bicarbonate loss and
administering physiologic saline.
Urinary diversionrelated disorders may require thiazide
therapy or alkali supplements.
The most common clinical form of acid ingestion occurs in
patients receiving hyperalimentation. Treatment is to adjust
composition of the parenteral nutrition.
Table 3. Causes of Metabolic Acidosis With Normal

Anion Gap
Nonrenal
Diarrhea
Pancreatic fistula
Urinary diversion
Acid ingestion
Arginine infusion
Renal
Uremia
Proximal RTA
Hypokalemic distal RTA
Classic
Amphotericin-induced
Hyperkalemic distal RTA
Short-circuit distal RTA
Urinary tract obstruction
Sickle cell disease
Drug-induced
Mineralocorticoid deficiency
Addison disease
Selective aldosterone deficiency
Hyporeninemic hypoaldosteronism
RTA, renal tubular acidosis.
From Laski ME, Kurtzman NA. Acid-base disorders in medicine. Dis Mon.
1996;42:90-125. Used with permission.
424
III DISEASES
Renal
Proximal RTA (type 2) occurs because the proximal tubule
fails to reclaim bicarbonate appropriately.
It occurs in isolation or as part of Fanconi syndrome
(aminoaciduria, phosphaturia, uricosuria, glycosuria, and
bicarbonaturia).
Proximal RTA is unusual and occurs most commonly as
part of Fanconi syndrome that may be caused by Wilson
disease, heavy metals, autoimmune diseases, amyloidosis,
multiple myeloma, transplant rejection, nephropathy,
paroxysmal nocturnal hemoglobinuria, gentamicin, ifosfamide, and other conditions.
Often, treatment is not required, but if acidosis is severe,
bicarbonate or a thiazide plus bicarbonate is recommended.
In classic distal RTA (type 1), hyperchloremic, hypokalemic
metabolic acidosis, H+ secretion in the collecting ducts or the
ability to lower urinary pH is impaired.
Several subtypes have been identified.
Causes of distal RTA include autoimmune disorders, cirrhosis, medullary sponge kidney, systemic lupus erythematosus, sickle cell anemia, obstructive uropathy, renal
transplantation, amphotericin, lithium, analgesic nephropathy, and drug toxins.
Hyperkalemic distal RTA (type 4) is caused by defective
ammonia production.
Most patients with RTA type 4 have hyporeninemic hypoaldosteronism.
Usual causes include diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathies, and NSAIDs.
Without a clear or reversible cause, the treatment of distal
RTA relies on providing alkali.
In patients with hyperkalemic distal RTA, potassium
restriction is necessary; if aldosterone is absent, fludrocortisone can be used.
METABOLIC ALKALOSIS
Metabolic alkalosis occurs when bicarbonate accumulates
or acid is lost from the body.
425
Three major causes of metabolic alkalosis: volume contraction,

mineralocorticoid excess, and alkali administration (Table 4)
Management
For patients with metabolic alkalosis, the history and physical exam should focus on eating habits, drug use, and volume status.
A low urinary chloride (<20 mEq/L) suggests volume contraction.
For volume contraction, therapy focuses on repairing any
volume losses and potassium deficiency with the use of
physiologic saline and potassium supplementation.
For nonvolume-depleted patients, treatment aims at correcting steroid excess if possible. Spironolactone, up to 400
mg daily, with large amounts of potassium may be considered for some patients.
For alkali load syndrome, alkalemia should resolve after the
exogenous source of alkali is stopped.
RESPIRATORY ACIDOSIS
Respiratory acidosis is characterized by a decrease in alveolar ventilation relative to carbon dioxide production.
Table 4. Causes of Metabolic Alkalosis

Volume contraction (urinary [Cl] <20 mEq/L)
Emesis
Gastric suction
Diuretics
Posthypercapnia
Without volume contraction (urinary [Cl] >20 mEq/L)
Primary & secondary mineralocorticoid excess
Cushing syndrome
Errors of steroid metabolism
Liddle syndrome
Bartter syndrome
Iatrogenic hypermineralocorticoidism
Alkali loads (no volume contraction)
Milk-alkali syndrome
Bicarbonate administration
Lactate or citrate administration
Modified from Laski ME, Kurtzman NA. Acid-base disorders in medicine.
Dis Mon. 1996;42:90-125. Used with permission.
426
III DISEASES
Respiratory acidosis appears to be caused by a primary

increase in blood PCO2.
Management
The problem for most patients with respiratory acidosis is not
acidosis but hypoxia of respiratory failure.
Hypercapnia can result from an acute or chronic process.
Acute hypercapnia develops as a consequence of pneumonia, status asthmaticus, central nervous system depression, and neuromuscular impairment.
Treatment should focus on correcting the hypoxia, by
mechanical ventilation if necessary, and removing or
improving the underlying cause.
Chronic hypercapnia results from many conditions, including COPD, neuromuscular disorders, and chest wall
problems.
The acidosis is usually well buffered, the decrease in pH
is of no consequence, and no treatment is needed
regarding pH. However, sometimes, an acute respiratory
decompensation (most commonly from pneumonia,
Table 5. Causes of Respiratory Acidosis

Abnormal respiratory driveexcessive sedation, central alveolar
hypoventilation, sleep apnea
Neuromuscularmyasthenia gravis, paralytic agents, multiple sclerosis, amyotrophic lateral sclerosis, Guillain-Barr syndrome, botulism, myopathies, myositis
Thoracic cage problemsscoliosis, ankylosing spondylitis, flail chest
Obstructive diseasetracheal, laryngeal, or bronchial obstruction;
obstructive sleep apnea
Pulmonary diseasesevere interstitial fibrosis, COPD
Pleural diseasefibrothorax, hydrothorax, pneumothorax
Ventilator-management errorsexcessive dead space, insufficient
tidal volume and/or ventilator rate
Data from Laski ME, Kurtzman NA. Acid-base disorders in medicine. Dis
Mon. 1996;42:90-125; Narins RG, Emmett M. Simple and mixed acid-base
disorders: a practical approach. Medicine (Baltimore). 1980;59:161-87.
427
sedation, or uncontrolled oxygen therapy) superimposes the chronic hypercapnia, producing more retention of carbon dioxide and more acidosis.
Management depends on severity of the acute process
and baseline situation of the patient.
Management usually includes antibiotics, bronchodilators, aspiration of secretions, and, if due to excessive sedation, naloxone or flumazenil could be helpful.
The minimum amount of oxygen to keep the PO2 about
60 mm Hg should be applied and mechanical ventilation should be used with a conservative approach
because of the great difficulty in weaning such patients
from ventilators.
If the patient is encephalopathic from hypercapnia,
mechanical ventilation should be instituted.
Note: when a patient with chronic hypercapnia is on
mechanical ventilation, the goal PCO2 is needed to keep a
normal pH (not a normal PCO2), because, rapid PCO2
reduction produces posthypercapnic alkalosis, with potentially serious consequences.
RESPIRATORY ALKALOSIS
Respiratory alkalosis is characterized by an increase in alveolar ventilation relative to carbon dioxide production.
Respiratory alkalosis appears to be caused by a primary
decrease in blood PCO2.
Management
Respiratory alkalosis is the most common acid-base disorder.
Respiratory alkalosis of <24 hours is considered acute.
Treatment should be directed toward decreasing hyperventilation and correcting the underlying cause.
Most cases of respiratory alkalosis, especially chronic cases,
pose little risk to health and are not treated.
In psychogenic respiratory alkalosis, such as panic attacks,
management includes reassurance, psychologic therapy,
rebreathing into a bag, and sometimes sedation.
428
III DISEASES
Table 6. Causes of Respiratory Alkalosis
Hypoxia
Pulmonary receptor stimulationpneumonia, pulmonary embolism,
asthma, pulmonary edema, restrictive disorders
Psychogenic
Drugstheophylline, salicylates, progesterone
Central nervous systemCheyne-Stokes breathing, stroke,
infection
Cirrhosis
Pregnancy
Fever
Sepsis
Hyperthyroidism
Errors in ventilator settingsexcessive tidal volume, excessive
ventilation rate
Modified from Laski ME, Kurtzman NA. Acid-base disorders in medicine.
Dis Mon. 1996;42:90-125. Used with permission.
429
III DISEASES
ACUTE CORONARY SYNDROMES
Arjun Deb, M.D.
DEFINITIONS
Acute coronary syndromes include
Unstable angina
NonST-segment elevation myocardial infarction
(NSTEMI)
ST-segment elevation myocardial infarction (STEMI)
Unstable Angina
Clinical syndrome resulting from rupture of an unstable
plaque or from a critically stenotic stable plaque
It is defined by any of the following:
Rest anginaangina occurring at rest and usually lasting
>20 minutes within a week before presentation
New-onset anginaangina of at least Canadian
Cardiovascular Society class III severity within 2 months
before initial presentation
Worsening anginapreviously diagnosed angina that is
more frequent, longer in duration or lower in threshold, and
has worsened by at least one class within 2 months after
initial presentation to at least Canadian Cardiovascular
Society class III severity
Myocardial Infarction
Diagnosed by the presence of at least two of the following
three criteria:
Prolonged chest pain (>30 minutes) or anginal equivalent
Special abbreviations used in this chapter: LBBB, left bundle branch block;
LMWH, low-molecular-weight heparin; NSTEMI, nonST-segment elevation
myocardial infarction; PCI, percutaneous coronary intervention; PTCA, percutaneous transluminal coronary angioplasty; STEMI, ST-segment elevation
myocardial infarction; tPA, tissue plasminogen activator.
431
ECG changes consistent with injury or necrosis

Increased levels of cardiac enzymes
Subdivisions
NSTEMIcharacterized by an increase in troponin I or T in
the clinical setting of acute coronary syndrome and/or STsegment depression >1 mm in two or more contiguous leads
STEMIcharacterized by ST-segment elevation >1 mm
in two or more contiguous leads or left bundle branch
block (LBBB) not known to be old
Unstable angina cannot be distinguished from NSTEMI at
presentation.
CLINICAL PRESENTATION
Chest pain is the most common presenting symptom of acute
coronary syndromes.
Chest pain is more likely due to an acute coronary syndrome if
It is more severe than previous typical episodes of angina.
It lasts >20 minutes but <4 hours.
It started at rest.
It radiates and is accompanied by dyspnea, diaphoresis,
nausea, or vomiting.
Chest pain is more likely to be noncardiac related if:
Sharp pain worsened by coughing or deep breathing
Brief episodes of pain lasting a few seconds
Constant pain lasting >8 hours to days
Pain located solely in the middle or lower abdominal region
Pain reproduced by palpation or movement of chest wall
or localized with a finger
Other less common presenting symptoms of acute coronary
syndrome
Loss of consciousness
Sudden onset of dyspnea
Altered mental status
Appearance of an arrhythmia (atrioventricular block, atrial fibrillation, ventricular tachyarrhythmias)
Unexplained hypotension
Physical findings indicating a high likelihood of an acute
coronary syndrome and high cardiovascular risk include
Hypotension
Third heart sound
Increased jugular venous pressure
432
III DISEASES
Apical systolic murmur of transient mitral regurgitation
Pulmonary rales indicative of pulmonary edema
The likelihood of coronary artery disease in patients with
symptoms suggesting unstable angina is outlined in Table 1
and the short-term risk of death or nonfatal myocardial infarction in Table 2.
Aim of the initial history and physical examination should be
Assess the likelihood of coronary ischemia as the cause of
chest pain
Exclude other life-threatening disorders such as pulmonary
embolism and aortic dissection, which may have a similar
presentation
Assess the severity of the acute coronary syndrome and
provide appropriate triage
ECG AND LABORATORY DIAGNOSIS OF ACUTE

CORONARY SYNDROME
ECG Findings
Unstable Angina
Nonspecific findings are the most common.
ECG may be normal in up to 40% of cases.
Transient T-wave inversion is the most sensitive sign for ischemia.
Transient flat or downsloping ST-segment depression is the
most specific sign for ischemia and may represent subepicardial injury.
NSTEMI
Absence of ST-segment elevation
Nonspecific changes are most common.
Persistent ST-segment depression with T-wave inversion is
the most specific sign.
STEMI
ST-segment elevation >1 mm (defined as elevation of the
ST segment >1 mm 0.6 millisecond after the J point) in two
or more contiguous leads (i.e., leads that represent a myocardial wall, I, aVL-lateral wall; II, III, aVF-inferior wall)
LBBB not known to be old
433
434
Table 1. Likelihood of Coronary Artery Disease (CAD) in Patients With Symptoms Suggestive of Unstable Angina
High likelihood (0.85-0.99)
Intermediate likelihood (0.15-0.84)
Low likelihood (0.01-0.14)
Any of the following features:

Absence of high-likelihood features & any Absence of high- & intermediate-likelihood features & any of the following:
History of previous MI, sudden death,
of the following:
CABG, or known CAD
Definite angina in men <60 or women
Probably not angina
One risk factor other than diabetes
Definite angina in men >60 or women
<70 years
>70 years
Probable angina in men >60 or women
T-wave inversion or flattening <1 mm
Transient hemodynamic or ECG
>70 years
in leads with dominant R waves
changes with pain
Chest pain probably not angina in
Normal ECG
Variant angina
diabetics
ST-segment elevation/depression >1 mm
Chest pain probably not angina with
Marked symmetrical T-wave inversion
2 or more risk factors other than
in multiple precordial leads
diabetes
ST-segment depression 0.05-1.0 mm
T-wave inversion 1 mm in leads with
dominant R waves
Extracardiac vascular disease
CABG, coronary artery bypass graft; MI, myocardial infarction.
Modified from ACC/AHA Practice Guidelines [cited 2005 Nov 3]. Available from http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm.
Used with permission.
Table 2. Short-Term Risk of Death or Nonfatal Myocardial Infarction in Patients With Unstable Angina
High risk
At least 1 of the following has to be
present:
Prolonged (>20 minute) ongoing
chest pain
Pulmonary edema
Angina with S3 or new/worsening rales
Angina with hypotension
Angina with new/worsening mitral
regurgitation murmur
Angina at rest with dynamic ST
changes >1 mm
Low risk
Absence of any high- or
intermediate-risk feature
Increased angina, frequency,
severity, duration
Angina provoked at lower
threshold
New-onset angina with onset
2 weeks to 2 months before
presentation
Normal or unchanged ECG
CAD, coronary artery disease; CCSC, Canadian Cardiovascular Society Class; S3, third heart sound.
Modified from ACC/AHA Practice Guidelines [cited 2005 Nov 3]. Available from http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Used with permission.
435
III DISEASES
Intermediate risk
Absence of any high-risk features &
any of the following:
Prolonged angina at rest >20 minutes,
now resolved in a person with
moderate/high likelihood of CAD
Rest angina >20 minutes or resolved
with rest or nitroglycerin
Nocturnal angina
Angina with dynamic T-wave changes
New-onset CCSC III/IV angina in
past 2 weeks with moderate/high
likelihood of CAD
Pathologic Q waves or resting STsegment depression <1 mm in
multiple leads
Laboratory Findings
Elevation of CK, CK-MB, and troponin
Myocardial necrosisWhether this is acute coronary syndrome will depend on clinical setting.
Other possibilities include
Myocarditisseptic, viral, inflammatory, paraneoplastic
Trauma
Systemic inflammatory response syndrome
Catastrophic pulmonary embolism
Increase in CK and CK-MB with normal levels of troponins
Early myocardial injury if this only happens initially when
there was not enough time for troponins to increase, but
troponin levels should be increased on further testing.
Persistent increase in CK with normal troponin is found in
rhabdomyolysis and severe skeletal muscle injury or necrosis.
Increased troponins with normal CK and CK-MB
Uncertain pathophysiologic situation, which clinically
indicates increased risk for death
If chest pain is present and patient is at obvious risk for
coronary artery disease, manage as acute coronary
syndrome.
Other possibilities include
Pulmonary embolism
Severe systemic illness
Renal failure (troponin T rather than I is more commonly affected by renal function)
EARLY RECOGNITION OF MYOCARDIAL INFARCTION
Advise patients prescribed nitroglycerin to call 911 after
1 nitroglycerin if no improvement in chest pain after 5
minutes.
Family members should be trained in cardiopulmonary resuscitation and use of automatic external defibrillators.
PERIHOSPITAL ISSUES
After onset of chest pain, patient chews 162 or 325 mg aspirin.
Advance cardiac life support providers or paramedics perform, interpret, relay 12-lead ECG to hospital.
Prehospital thrombolysisphysician in ambulance or fulltime paramedics who are able to transmit ECGs and are in
contact with trained medical personnel
436
III DISEASES
Patients <75 years with STEMI and shock should be transported to hospital with percutaneous coronary intervention
(PCI) capability, with door-to-door transfer time <30 minutes
(same for patients with congestive heart failure).
MANAGEMENT OF ACUTE CORONARY SYNDROMES

Immediate Assessment and Treatment
The following assessment should be completed within the first
10 minutes:
Vital signs, including oxygen saturation
IV access
12-lead ECG
Brief targeted history and physical as discussed above,
including contraindications to thrombolytic therapy
Initial cardiac marker levels
Initial coagulation and electrolyte levels
Possible chest X-ray (<30 minutes)
The patient should also receive the following during the initial assessment:
Oxygen at 4 L/minute
Aspirin 325 mg chewable
Nitroglycerin sublingual or spray
Morphine IV if pain not relieved by nitroglycerin
Specific Management
Unstable Angina and NSTEMI
Rapid initiation of antithrombotic and antianginal therapy
is the goal of management of acute coronary syndromes.
Aspirin
All patients with suspected unstable angina should receive 325
mg of crushed aspirin initially, followed by 160-325 mg
daily.
For patients with unstable angina, aspirin has been found to
decrease the incidence of death and nonfatal myocardial
infarction by 50%.
Clopidogrel is recommended for patients who have hypersensitivity to aspirin.
437
-Blockers
All patients with an acute coronary syndrome should receive
-blockers.
Metoprolol, 5 mg IV at 5- to 10-minute intervals, followed by oral metoprolol 25-50 mg every 6-12 hours.
Titrate the dose to desired heart rate and blood pressure.
If there is absolute contraindication, use diltiazem or
verapamil.
The goal is to relieve cardiac ischemia and decrease the resting heart rate to 50-60 beats/minute and a mean arterial pressure of 60-70 mm Hg.
Heparin
The combination of unfractionated IV heparin and aspirin is
superior to aspirin alone (reducing the risk of death and
myocardial infarction by 33%).
Low-molecular-weight heparin (LMWH) is as effective as
unfractionated heparin, without causing excess bleeding
complications.
Heparin should be continued for a minimum of 3-7 days
because its beneficial effects are lost if infusion is discontinued after 2 days.
If the patient is triaged to early invasive therapy, unfractionated heparin is preferred because it can be reversed
quickly.
For patients with a history of heparin-induced thrombocytopenia, give lepirudin, a direct thrombin inhibitor.
Heparin, IV bolus 80 U/kg, followed by 18 U/kg per hour
Adjust infusion rate to keep aPTT at 2-2.5 the upper
limit of normal.
Check aPTT 6 hours after starting heparin infusion and 6
hours thereafter until the goal aPTT is reached, then check
every 12-24 hours.
Heparin normograms are helpful in adjusting infusion rates.
Enoxaparin, 1 mg/kg every 12 hours. Dalteparin, 120 U/kg
every 12 hours, is as effective without having to monitor
serial aPTT.
Lepirudin, 0.4 mg/kg bolus, followed by 0.15 mg/kg per
hour infusions with a goal aPTT of 1.5-2.5 the upper limits
of normal
438
III DISEASES
Glycoprotein IIb/IIIa Receptor Inhibitors
They inhibit cross linking of platelets and prevent platelet
aggregation and thrombus formation.
In patients with unstable angina and NSTEMI, eptifibatide
added to heparin and aspirin reduced the absolute risk of
death and nonfatal myocardial infarction at 30 days by 5%,
when compared with heparin and aspirin.
Compared with heparin alone, tirofiban and heparin reduced
the relative risk of death, nonfatal myocardial infarction, and
refractory ischemia at 7 days by 32%.
Abciximab should only be given to patients undergoing early
revascularization.
Currently, eptifibatide and trofiban are recommended in
addition to heparin and aspirin for patients with unstable
angina or NSTEMI who have high-risk characteristics as
defined by the TIMI Risk Score or in whom PCI is
planned.
Eptifibatide, 180 g/kg bolus, followed by 2 g/kg per minute
for 24-48 hours
Tirofiban, 0.4 g/kg per minute over 30 minutes, followed by
0.1 g/kg per minute for 24-48 hours
Abciximab, 0.25 mg/kg IV bolus, followed by 10 g/minute
for 12 hours for unstable angina and planned PCI
Clopidogrel
It is a thienopyridine that inhibits the adenosine diphosphatemediated activation of platelets.
Clopidogrel decreased the rate of major adverse cardiovascular events by 20% in patients admitted with an acute
coronary syndrome in the CURE study. In that study,
however, patients were not offered early revascularization strategy and not treated with glycoprotein IIb/IIIa
inhibitors.
Currently, the use of clopidogrel in NSTEMI acute coronary
syndrome should be limited to patients not undergoing early
revascularization in whom glycoprotein IIb/IIIa inhibitors
are not used.
439
Statins
HMG-CoA reductase inhibitors have benefits other than
lipid-lowering effects in patients with an acute coronary
syndrome.
PROVE-IT trial showed that lowering low-density
lipoprotein cholesterol to mean of 65 mg/dL in hospitalized patients with high-risk coronary syndromes produced a 16% relative risk reduction in combined end
point of death from any cause, myocardial infarction,
recurrent unstable angina, or revascularization at 2 years.
Therefore, we recommend treating patients with acute
coronary syndrome to low-density lipoprotein cholesterol of <80.
The MIRACLE study showed evidence that statins diminish
the rate of recurrent ischemia after an acute coronary
syndrome.
Aldosterone Blockers
Eplerenone 50 mg/day, when started within 3-14 days after
myocardial infarction in patients with a left ventricular ejection fraction <40%, reduced morbidity and mortality at 3
months and 2 years compared with placebo.
Nitrates
They decrease cardiac ischemia and anginal pain by reducing preload and dilating coronary arteries.
Sublingual nitroglycerin should be administered immediately to patients with an acute coronary syndrome.
IV infusion can be used for refractory pain or initially for
patients who are hypertensive on presentation.
Tachyphylaxis may develop within 24 hours after a continuous infusion.
Nitroglycerin, 0.4 mg sublingually, can be given at presentation, and IV nitroglycerin can be started at 10-20 g/minute
and rapidly titrated to decrease pain.
Morphine
Pain relief is an important therapeutic goal, and patients
should receive morphine frequently for pain relief.
Morphine, 1-3 mg IV every 5-10 minutes until pain is
relieved
440
III DISEASES
Oxygen
All patients with a suspected acute coronary syndrome should
receive oxygen, especially if they have respiratory distress or
hypoxemia.
Oxygen saturation should be kept >90%.
Oxygen, 2-4 L, to keep arterial oxygen saturation >90%
Early Percutaneous Revascularization
Patients with high and intermediate TIMI risk scores benefit from early revascularization with PCI (<48 hours after
admission), according to the FRISC II and TIMI 18 trial
results (Table 3).
STEMI
Emergency department
Door-to-ECG review <10 minutes
Right-sided ECG leads for all inferior STEMI patients
Table 3. TIMI Risk Factor Score*

Risk factor score
1. Age >65 years
2. Three or more risk factors for coronary artery disease
3. Previous coronary stenosis >50% or previous percutaneous
coronary intervention
4. Two or more anginal events over the past 24 hours
5. ASA use in the past 7 days
6. ST-segment changes
7. Cardiac markers elevation
Risk of adverse cardiac event
No. of risk factors
Risk, %
0-1
4.7
2
8.3
3
13.2
4
19.9
5
26.2
6-7
41.0
*Low risk = score 0-2; intermediate risk = score 3-4; high risk = score 5-7.
Patients with elevated cardiac enzymes and/or ST changes should be included in the high-risk category independent of their overall score.
Myocardial infarction, cardiac death, or recurrent ischemia.
441
Door-to-percutaneous transluminal coronary angioplasty

(PTCA) time <90 minutes for primary PCI
Goal of managementimmediate reperfusion of the infarctrelated artery with reestablishment of TIMI grade 3 flow
TIMI flow gradesTIMI 0 = complete occlusion of infarctrelated artery, TIMI 1 = flow into but not through the
obstructive thrombus, TIMI 2 = reperfusion of infarct-related
artery with slow flow, TIMI 3 = normal brisk flow.
Initial emergency department management
Aspirin: patient chews 162 or 325 mg
-Blocker
PO
IV, especially if hypertension or tachycardia
Reperfusion Therapy
Reperfusion therapy can be accomplished with either thrombolytics or percutaneous coronary intervention (which
includes the use of stents).
The choice of reperfusion therapy depends on availability
of treatment modalities; ACC/AHA guidelines recommend
that thrombolytics be given within 30 minutes after diagnosis
or PCI be performed within 90 minutes after diagnosis.
The GUSTO IIb trial showed that PTCA reduced the combined end point of death, nonfatal myocardial infarction, or
nonfatal disabling stroke (13.7% for tissue plasminogen
activator [tPA] vs. 9.6% for PTCA) at 30 days, but these differences were nonsignificant after 6 months of follow-up.
PTCA with stenting decreases the rates of restenosis and
reocclusion more than angioplasty alone and may prevent
the loss of benefit over time seen in earlier trials.
Thrombolysis
All patients with new LBBB or ST-segment elevation >1
mm in two contiguous leads are potential candidates for
thrombolytic therapy if they present within 12 hours after
onset of symptoms.
ISIS-2 showed a mortality benefit with thrombolytics compared with placebo of about 20% at 30 days that persisted for
up to 10 years.
The maximal benefit was in people with anterior wall
infarction.
442
III DISEASES
Reperfusion therapy
Fibrinolysis if no PCI within 90 minutes available, doorto-needle <30 minutes
Fibrinolysis if true posterior myocardial infarction
Absolute contraindications to fibrinolysis
Any previous intracranial hemorrhage
Any cerebral aneurysm, arteriovenous malformation,
or malignant neoplasm
Stroke within last 3 months (except last 3 hours)
Active bleeding
Suspected aortic dissection
Notable head or facial trauma within last 3 months
History of stroke more than 3 months ago is now a relative contraindication.
The presence of any one of these contraindications also contraindicates PCI, which requires full anticoagulation with
heparin, glycoprotein IIb/IIIa inhibitors, clopidogrel, and
aspirin.
GUSTO I showed that tPA decreased 30-day mortality by
15% compared with streptokinase.
Currently, tenecteplase-tPA is the thrombolytic agent of choice,
as it can be given as a one-time bolus with heparin and aspirin.
Determining whether reperfusion therapy is successful is
difficult clinically. The combination of chest pain relief, at
least a 50% decrease in ST-segment elevation, and the appearance of accelerated idioventricular rhythm predicts successful
reperfusion with high specificity.
Complete resolution of ST-segment elevation at 90 minutes
indicates a 93% likelihood of reperfusion of the infarct-related artery and an 80% likelihood of TIMI grade 3 flow.
Patients who receive thrombolytic therapy and do not have
complete resolution of chest pain or a 50% decrease in STsegment elevation at 60 minutes should be referred for rescue
PCI.
1
Combination 2-dose tenecteplase or reteplase with abciximab for those <75 years
1
Combination 2-dose lysis and glycoprotein IIb/IIIa inhibitors
is contraindicated for those >75 years
443
Alteplase (recombinant tPA), IV bolus of 15 mg, followed by

0.75-mg/kg (up to 50 mg) IV infusion over 30 minutes, then
0.25-mg/kg (up to 35 mg) IV infusion over 60 minutes, with
a total maximal dose of 100 mg over 90 minutes.
The risk of serious intracranial bleeding is about 0.7% for
patients receiving tPA, with a mortality rate >50% if bleeding occurs and higher among patients >75 years.
PCI
Addressing nonculprit lesions in primary PCI is a class III
indication and should not be done routinely.
Randomized controlled clinical trials show that PCI offers
better TIMI grade 3 flow, more sustained patency of the
infarct-related artery, and fewer bleeding complications than
thrombolytic therapy.
Thirty-day and long-term mortality also favor PCI in comparison with thrombolytic therapy, and PCI is the reperfusion modality of choice at our and most major institutions
in the U.S.
The door-to-PTCA time should be <60-90 minutes.
If symptoms are <3 hours, primary PCI is preferred if
expected door-to-PTCA time minus expected door-to-needle
time is <60 minutes.
Primary PCI is preferred
Congestive heart failure or shock
Symptom duration >3 hours
Nonculprit vessels should not be treated at time of primary PCI
Rescue PCI if hemodynamically or electrically unstable or
if persistent ischemia
Routine coronary angiography and PCI if indicated by flowlimiting lesion post-lysis in stable patients
Glycoprotein IIb/IIIa inhibitors such as abciximab or integrilin
should be administered routinely during PCI to decrease the
rate of death and recurrent myocardial infarction, as shown
in the CADILLAC and ADMIRAL trials.
Primary PCI is also the treatment of choice for STEMI complicated by cardiogenic shock.
The SHOCK trial showed a 1-year survival of 47% in the
early revascularization group and 33% in the medical stabilization group.
444
III DISEASES
Coronary Artery Bypass Surgery
Emergency bypass surgery is indicated for left main coronary
artery disease or severe three-vessel disease not amenable
to percutaneous revascularization.
Diabetic patients with three-vessel disease appear to have
better survival if they undergo surgical bypass.
For those in whom the left coronary anterior artery is not
bypassed, survival benefits are unproven.
Timing of coronary artery bypass graft
Critical anatomy with preserved left ventricular function
perform coronary artery bypass graft before dismissal
If significant left ventricular dysfunctiondelay performing coronary artery bypass graft
Anti-ischemic Therapy
Aspirin, nitrates, -blockers, statins, oxygen, and morphine
should be administered as for treatment of unstable angina
and NSTEMI (see above).
Unlike their role in unstable angina, -blockers have been
conclusively proven to decrease the mortality rate and occurrence of major cardiovascular events after acute myocardial
infarction.
Antithrombotic Therapy
Heparin should be given as adjunctive therapy after thrombolytic therapy.
Enoxaparin is contraindicated with lysis in patients
>75 years
With increased creatinine (2.0 mg/dL in women, 2.5 mg/dL
in men)
Preferably, a weight-based nomogram should be used.
For patients undergoing direct angioplasty, heparin should be
given in combination with glycoprotein IIb/IIIa inhibitors.
Angiotensin-Converting Enzyme Inhibitors

Analysis of pooled data shows that angiotensin-converting
enzyme inhibitors started within 36 hours after myocardial
445
infarction significantly decreased 30-day mortality (RRR

= 7%).
Most of this benefit was observed in the first 7 days after
myocardial infarction and in high-risk groups such as Killip
classes II and III and anterior wall myocardial infarction.
Angiotensin-converting enzyme inhibitors should be started
at the lowest possible dose and titrated up as tolerated.
Angiotensin-converting enzyme inhibitor in first 24 hours
for
Anterior myocardial infarction
Left ventricular ejection fraction <0.40
Heart failure
Angiotensin receptor blocker (valsartan or candesartan) if
patient cannot tolerate angiotensin-converting enzyme
inhibitor
Other Adjunctive Measures

There is no role for the routine use of antiarrhythmic agents
or magnesium or calcium channel blockers unless specifically
indicated.
Aggressive blood sugar control has a beneficial effect on the
outcome of patients with myocardial infarction.
Measure left ventricular function in all infarct patients
Implantable Cardioverter-Defibrillator
Ventricular fibrillation or significant sustained ventricular
tachycardia >48 hours after STEMI, not due to recurrent
ischemia or reinfarction
One month after STEMI if left ventricular ejection fraction
is 0.31-0.40 with nonsustained ventricular tachycardia and
with inducible ventricular tachycardia or ventricular fibrillation at electrophysiologic study
One month after STEMI with left ventricular ejection fraction <0.31
446
Chest pain suggestive

of coronary ischemia
12-lead ECG
or new LBBB
ECG with ST-segment

depression & T-wave
changes strongly suspicious
for ischemia
Admit patient
Continue emergency room

evaluation; serial ECG &
cardiac markers
Consider 2D echocardiography
Anti-ischemic therapy,
consider ACE inhibitor
Evidence of
ischemia/infarction
Assess contraindications to
thrombolysis
Anti-ischemic
therapy, ACE
inhibitor
Normal/nondiagnostic ECG
Pain free
Yes
Conservative strategy
No
No
Yes
Discharge in 812 hours
Admit
Early catheterization
Revascularization if
indicated
Routine blood tests at

admission: CBC, electrolytes,
lipid panel
447
Initiate reperfusion therapy if

ST-segment elevation develops
III DISEASES
Thrombolysis within 30 minutes

of arrival or patient taken to
cath lab within 60 minutes
after arrival
Fig. 1. Algorithm for management, in the emergency department, of patients with suspected
myocardial infarction. ACE, angiotensin-converting enzyme; LBBB, left bundle branch
block.
448
Aspirin, -blocker, IV
nitroglycerin, oxygen,
morphine
Fig. 2. Algorithm for the management of Q< 12 hours
Not candidate
for reperfusion
Eligible for
thrombolytic
therapy
Persistent symptoms
Thrombolytics
contraindicated
No
Frontloaded tPA
wave myocardial infarction. ACE, angiotensinconverting enzyme; tPA, tissue plasminogen

activator. (Modified from Antman EM.
Medical therapy for acute coronary syndromes:
an overview. In Braunwald E, editor. Atlas of
heart diseases. Vol VIII. St. Louis: Mosby;
1996. p. 10.1-10.25. Used with permission.)
>12 hours
Primary
angioplasty or
bypass surgery
Yes
Consider
reperfusion
therapy
Medical therapy, ACE
inhibitors, statins,
oral nitrates
A
Acute coronary syndrome

ECG, cardiac enzymes
No ST-segment elevation
High risk
Low risk
Intermediate risk
Admit to CCU
or telemetry
Cath lab available
Treat with aspirin,

heparin, abciximab,
anti-ischemics
Admit to CCU
Treat with aspirin,
heparin, tirofiban
& anti-ischemics
Treat with aspirin, heparin, & anti-ischemics

No glycoprotein IIb/IIIa inhibitor
Admit to CCU
Treat with aspirin,
heparin, tirofiban
& anti-ischemics
Defer PCI
Noninvasive risk
stratification
Exercise myocardial
perfusion imaging
Pharmacologic stress with perfusion

imaging or dobutamine stress
echocardiography
Inducible ischemia
449
Secondary prevention with aspirin, -blocker, ACE inhibitor, & statin
No ischemia
III DISEASES
Urgent PCI with intent

to insert stent
Cath lab not available
Fig. 3. Algorithm for the

management of unstable
angina/ NSTEMI. ACE,
angiotensin-converting
enzyme; CCU, coronary
care unit; PCI, percutaneous
coronary intervention.
III DISEASES
ACUTE RENAL FAILURE
Andrew D. Rule, M.D.
DEFINITION
Acute renal failure (ARF) is an increase in the serum level
of creatinine of 0.5 mg/dL daily or BUN of 10 mg/dL daily
over several days, with a decrease in glomerular filtration
rate.
Pseudoacute renal failure can occur when there is an increase
in creatinine or BUN without a decrease in the glomerular filtration rate.
Increased creatinineincrease in protein intake, part of
rhabdomyolysis, trimethoprim, cefoxitin, flucytosine.
Increased BUNgastrointestinal tract bleeding, tissue
trauma, glucocorticoids, tetracycline.
CLASSIFICATION
Acute vs. Chronic
Chronic renal failure is suggested by
Electrolyte abnormalitieshypocalcemia and hyperphosphatemia with high level of parathyroid hormone.
High levels of creatinine and BUN without symptoms of
uremia
Anemia with low erythropoietin levels
Osteodystrophy and neuropathy
Abnormal renal ultrasound with
Small kidneys (<10 cm)
Decreased or absent renal cortex
Increased echogenicity of renal cortex
Urine Output
Anuric (<50 mL/day)
Special abbreviation used in this chapter: ARF, acute renal failure.

451
Limited differential diagnosiscomplete obstruction, rapidly progressive glomerulonephritis, cortical necrosis,

bilateral renal artery occlusion
Not typically seen in acute tubular necrosis
Oliguric (<400 mL/day)
Poor prognosis compared with nonoliguric
Nonoliguric (>800 mL/day)
ARF is also categorized by causeprerenal, intrinsic, and
postrenal
ETIOLOGY
The causes of ARF are listed in Table 1.
EPIDEMIOLOGY
Prevalence
ARF occurs in 1% of hospitalized patients and in 20% of
ICU patients.
In the community, ARF occurs in approximately 209 per 1
million population.
Risk Factors
Radiocontrast dye, especially patients with
Creatinine >2.0 mg/dL
Diabetes mellitus
Elderly
Hyperbilirubinemia
Mortality Rate
7% for ARF that is prerenal and leads to hospital admission
45% for ARF acquired in the hospital
70% for ARF acquired in the ICU
80% for postoperative ARF
ARF may present without any obvious signs or symptoms.
Typically, the precipitating condition (e.g., dehydration) suggests the need for a laboratory evaluation for ARF.
When ARF is severe and prolonged, a patient may present
clinically with volume overload (pulmonary edema, hypertension) and/or uremia, as in chronic renal failure.
Uremia symptoms include fatigue, lethargy, myoclonus,
452
III DISEASES
Table 1. Causes of Acute Renal Failure
Prerenal
Hypotensionany cause, e.g., sepsis
Hypovolemiacommon in elderly with baseline chronic renal
failure
Decrease in effective arterial blood volumecongestive heart
failure, nephrotic syndrome, cirrhosis, third spacing
Renal vasoconstrictionhypercalcemia, norepinephrine, epinephrine, cyclosporine, tacrolimus, amphotericin B, radiocontrast dye, cocaine
Drugs that impair renal vascular autoregulation (e.g., NSAIDs &
angiotensin-converting enzyme inhibitors)
Atheroembolic
Hepatorenal (diagnosis of exclusion)
Intrinsic
Glomerular or renal microvasculaturedisseminated intravascular coagulation, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, toxemia of pregnancy, glomerulonephritis
Acute tubular necrosis
Ischemic (from any prolonged prerenal process)
Medication- or toxin-inducedaminoglycoside antibiotics,
cisplatin, heavy metals, IV immune globulin, methotrexate,
foscarnet, pentamidine, organic solvents, cocaine, mannitol,
cyclosporine, tacrolimus, amphotericin B, radiocontrast dye
Intrinsic toxinsmyeloma light chain, uric acid, hemolysis,
rhabdomyolysis, oxalate
Allergic interstitial nephritis-lactams, sulfonamides,
trimethoprim, NSAIDs, ciprofloxacin, thiazide diuretics,
furosemide, rifampin, phenytoin, allopurinol
Chinese herb nephropathy (slimming teas)
Pyelonephritis
Infiltrateslymphoma, sarcoidosis
Renal allograft rejection
Postrenal
Ureteralpapillary necrosis, bilateral calculi, retroperitoneal
fibrosis, compression by tumor
Bladdercalculi, blood clot, neurogenic, transitional cell cancer
Medication-induced crystalluriaacyclovir, sulfonamides,
methotrexate, indinavir
Urethraprostate cancer, benign prostatic hypertrophy, stricture,
phimosis
Modified from Brady HR, Brenner BM. Acute renal failure. In: Braunwald
E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors.
Harrisons principles of internal medicine. 15th ed. New York: McGrawHill; 2001. p. 1541-51. Used with permission.
453
muscle cramps, uremic frost, seizures, pericarditis, arrhythmias, pruritus, ecchymoses, anorexia, nausea, bleeding,
hypothermia.
DIAGNOSTIC STRATEGIES
All patients with acute renal failure need the following diagnostic studies:
History and physical exam (Table 2)
CBC, creatinine, BUN, sodium, potassium, calcium, phosphorus (Table 3)
Urinalysis and fractional excretion of sodium (Table 4)
24-Hour creatinine clearance and proteinuria
For selected patients, antinuclear antibodies, antineutrophilic
cytoplasmic antibodies, anti-glomerular basement membrane
antibodies, cryoglobulins, others
Radiology
Renal ultrasound to evaluate for hydronephrosis (only 80%85% sensitive and serial studies may be necessary if suspicion for postrenal ARF is high)
Renal Doppler ultrasound to evaluate for renal artery stenosis and renal vein thrombosis
Bladder scan to evaluate for urethral obstruction
CT of retroperitoneum to evaluate for obstructing masses
In acute anuria, renal angiography should be considered to
rule out acute renal embolization.
Indications for Renal Biopsy

Generally not necessary in ARF except for following indications:
Suspicion of glomerulonephritis or vasculitis based on
serologic markers and/or urinalysis findings (RBC casts)
Exampleperinuclear antineutrophilic cytoplasmic
antibodies suggest microscopic polyangiitis, and biopsy confirms this with pauciimmune necrotizing glomerulonephritis.
Inconclusive clinical, lab, and radiology studies
Prerenal, postrenal, and toxin/ischemic acute tubular necrosis ruled out
Rule out allograft rejection vs. drug toxicity in renal transplant patients
454
III DISEASES
Table 2. History and Physical Exam Clues
Clue
Suggested cause
Recent angiography
Ischemia of extremity
Anuria
Rash, fever, arthralgias
Bone pain
Livedo reticularis, digit ischemia
Palpable purpura
Hemoptysis
Flank pain
Atheroemboli
Rhabdomyolysis
Postrenal
Allergic interstitial nephritis
Multiple myeloma
Atheroemboli
Vasculitis
Vasculitis
Renal artery occlusion, severe
glomerulonephritis, or pyelonephritis, nephrolithiasis
Papilledema
Malignant hypertension
Enlarged prostate
Benign prostatic hypertrophy
Anticholinergic medications
Neurogenic bladder
Alcoholic
Rhabdomyolysis
Prosthetic heart valve
Postinfectious glomerulonephritis
Chronic lymphocytic leukemia or Uric acid nephropathy
lymphoma or chemotherapy
Polyuria
Postrenal, hypokalemia
nephropathy
Abdominal pain, flank pain,
Postrenal
palpable bladder
Data from Brady HR, Brenner BM. Acute renal failure. In: Braunwald E,
Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors.
Harrisons principles of internal medicine. 15th ed. New York: McGrawHill; 2001. p. 1541-51.
Biopsy has <1% risk of serious complications (arteriovenous fistula, hematoma, infection, surgery, or death).
Biopsy alters management of patients in approximately three
of four cases.
MANAGEMENT
Treatment generally varies depending on the underlying cause.
PrerenalIncrease renal perfusion (IV fluids, blood transfusions, dopamine).
455
Table 3. Blood Tests

Suspected cause
Prerenal
Malignancy
Rhabdomyolysis
Multiple myeloma
Acute interstitial nephritis
Exogenous nephrotoxin (e.g.,
ethylene glycol)
Renal transplant rejection
Glomerulonephritis
Confirmatory
marker
BUN:creatinine ratio >20:1
Hypercalcemia & hyperuricemia
Increased CK level
Monoclonal gammopathy on SPEP
Eosinophilia
Osmolar gap
Immunosuppressive agent trough
level
ANA, ANCA, cryoglobulins, antiGBM antibodies, ASO titer
ANA, antinuclear antibodies; ANCA, antineutrophilic cytoplasmic antibodies; ASO, antistreptolysin O; GBM, glomerular basement membrane; SPEP,
serum protein electrophoresis.
PostrenalRelieve obstruction (place Foley catheter,

consult urology).
IntrinsicLook out for uremic complications and take
supportive measures.
GENERAL MEASURES
Check urinalysis, urine sodium, and urine creatinineimportant to check before IV fluids or diuretics.
Exclude postrenal and prerenal causes.
Consider a volume challenge if indicated.
Stop all nephrotoxic agents.
Consider furosemide.
Diuretics have not been shown to be advantageous in the
outcome of ARF but should be considered if patient is
volume overloaded or if toxins need to be excreted (e.g.,
heme pigments in rhabdomyolysis).
Treat with high dose of furosemide (100-200 mg IV 2 or 3
times daily).
Furosemide and/or mannitol drip may be helpful in obtaining diuresis.
Avoid doses of furosemide >600 mg/day because of ototoxicity.
Indications for dialysis in ARF are listed in Table 5.
456
Table 4. Urinalysis
Condition
Prerenal
Intrinsic
Acute GN
ATN
AIN
Postrenal
Sediment
Trace/no protein
Hyaline casts
>500
<1
Moderate-severe protein
Hemoglobin
Mild-moderate protein
Mild-moderate protein
Leukocytes
Hemoglobin
Trace/no protein
Leukocytes, mercury possible
RBCs, RBC casts

Dysmorphic RBCs
Granular casts
WBCs, WBC casts
RBCs, eosinophils
>500
<1
<350
<350
>1
>1
<350
>1
Crystals, RBCs
WBCs
Urine osmolality, mOsm/kg
AIN, acute interstitial nephritis; ATN, acute tubular necrosis; FENa, fractional excretion of sodium; GN, glomerulonephritis.
*FENa =
Urine Na plasma creatinine 100
Plasma Na urine creatinine

Modified from Thadhani R, Pascual M, Bonventri JV. Acute renal failure. N Engl J Med. 1996;334:1448-60. Used with permission.
FENa*
457
III DISEASES
Dipstick
SUPPORTIVE MEASURES
Nutritional management emphasizes sufficient calories without nitrogenous waste.
Calories between 126 and 147 kJ/kg daily
Protein between 0.6 g/kg and 1.4 g/kg daily
Restrict intake of fluid (1 L/day), sodium (90 mEq/day),
potassium (60 mEq/day), and phosphorus (800 mg/day).
Hyperkalemia
Check for ECG changes (peaked T waves or sinusoidal
pattern).
Treat with calcium gluconate, bicarbonate, insulin and
glucose, furosemide, sodium polystyrene sulfonate, and
dialysis.
Metabolic acidosis
Do not treat with sodium bicarbonate unless bicarbonate
decreases to <15 mmol/L or arterial pH is <7.2.
Indication for dialysis
Hypocalcemia
Does not require replacement unless severe
Hyperphosphatemia
Calcium acetate or sevelamer HCl (Renagel)
Stress ulcer prophylaxis
H2-Blockers
Adjust drug doses, especially digoxin, antibiotics, antihypertensives, and benzodiazepines.
Avoid NSAIDs and angiotensin-converting enzyme inhibitors.
Table 5. Indications for Dialysis in Acute Renal Failure

Oliguria or anuria
Creatinine increases >0.5 mg/dL daily for 2 consecutive days
BUN >100
Pulmonary edema unresponsive to diureticsurgent dialysis
Hyperkalemia (potassium >6.5), unresponsive to medical therapy
urgent dialysis
Symptomatic uremia such as pericarditis, bleeding, encephalopathyurgent dialysis
Severe metabolic acidosis unresponsive to medical therapyurgent
dialysis
458
III DISEASES
Prevention of Contrast-Induced Nephropathy
Prehydrate patient with IV fluids at 1-1.5 mg/kg per hour
for 8-12 hours before radiocontrast study.
Consider two doses of acetylcysteine 600 mg PO the day before
and the day of the radiocontrast study along with the IV fluids.
Ultrafiltration before and after contrast exposure
459
III DISEASES
ASTHMA
Jason Persoff, M.D.
Stephen F. Grinton, M.D.
DEFINITION
A chronic inflammatory disorder of the airways characterized
clinically by the following:
Intermittent, frequently entirely reversible, obstruction of
the airways
Generalized airway hyperreactivity
Absence of other diagnoses to account for these findings
Classification
Asthma is subdivided into several classes, or steps, based
on the following:
Subjective severity of patients symptoms
Objective measurements of lung function
A classification of asthma severity is given in Table 1.
ETIOLOGY
The epidemiologic features of asthma are listed in Table 2.
Risk Factors
Several different associations place persons at risk for the
development of asthma.
Known risk factors
Bronchial hyperresponsiveness
Atopy
Rhinitis with or without postnasal drip
Exposure to indoor allergens (particularly dust mites,
animal dander, mice, cockroaches, and fungi)
Exposure to outdoor allergens (particularly particulate
pollution)
Special abbreviation used in this chapter: PEF, peak expiratory flow.

461
462
Table 1. Classification of Asthma Severity*

Symptoms
Step 4: severe persistent
Step 3: moderate persistent
Step 2: mild persistent

Step 1: mild intermittent
Continuous symptoms
Limited physical activity
Frequent exacerbations
Daily symptoms
Daily use of inhaled short-acting
2-agonist
Exacerbations affect activity
Exacerbations 2 times a week,
may last days
Symptoms >2 times a week but
<1 time a day
Symptoms 2 times a week
Asymptomatic & normal PEF
between exacerbations
Exacerbations brief (from few hours
to few days), intensity may vary
Nocturnal symptoms
Lung function
Frequent
FEV1 or PEF 60% predicted

PEF variability >30%
>1 time per week
FEV1 or PEF >60% to <80% predicted

PEF variability >30%
>2 times per month

PEF variability 20%-30%
PEF variability <20%
2 times per month
FEV1, forced expiratory volume in 1 second; PEF, peak expiratory flow.

*A person should be assigned to the most severe grade in which any feature occurs.
A persons classification may change over time.
Patients at any level of severity can have mild, moderate, or severe exacerbations.
From the National Asthma Education and Prevention Program Expert Panel report 2: guidelines for the diagnosis and managemet of asthma. National
Heart, Lung, and Blood Institute [cited 2005 Aug 4]. Available from http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
III DISEASES
Table 2. Epidemiology of Asthma
Prevalence
Age-adjusted rate between ages 5 and 32 years49.4 per 1,000
persons in the general U.S. population
Incidence
Bimodal distribution
First peak between 4 & 10 years old
Second peak after 40 years old
Demographics
Sex
Age <20 (particularly during puberty), male predominance
Age 20-40, male female
Age >40, female predominance
Race
Blacks & Hispanics (especially in inner cities of U.S.) have
a greater prevalence of asthma than other ethnic groups
Geography
Countries with better housing construction have higher rates of
asthma
Link between asthma & airtight housing seen in industrialized areas
Higher rates in the U.S., U.K., New Zealand, & Australia
Lower rates in eastern and southern Europe, China
Atopy
Presence of IgE to specific allergens
Associated diseases
Rhinitis
Found in 80%-90% of patients with asthma regardless of
atopy status
Allergic rhinitis frequently precedes diagnosis of asthma
Aspirin sensitivity
Nasal polyps
Patients have pulmonary infiltrates, peripheral eosinophilia, & asthma
Gastroesophageal reflux disease
Genetics
Parental atopy & bronchial hyperresponsiveness
Increased risk of asthma in offspring of parents with atopy
(who do not have asthma)
If 1 parent has atopy and the other bronchial hyperresponsiveness, the risk of asthma increases substantially
463
Table 2 (continued)
Genes
Chromosome 5serum IgE level, eosinophil activation
& survival, bronchial hyperresponsiveness, & steroid
responsiveness
Chromosome 11-chain high-affinity IgE receptor
Mortality
Death rates
18.8 per 1 million people in general U.S. population
Higher rates & increasing rates in blacks
Respiratory syncytial virus

Maternal smoking during the in utero and childhood periods
Acute Asthma Exacerbations

Causes
Exposure to sensitizers at home or work
Respiratory infections
Cigarette smoke
Other environmental factors (e.g., cold or humidity)
Strong emotions
Menses
Inadequate asthma treatment
Ineffective asthma medication
Precipitating medications (e.g., aspirin or -blockers)
The classic triad of wheezing, cough, and dyspnea or worsening exercise tolerance lack sensitivity and specificity for
the diagnosis of asthma.
Objective testing is essential to confirm the diagnosis.
Increased risk for severe exacerbations
Known diagnosis of asthma
History of multiple asthma hospitalizations (particularly
ICU admissions)
History of refractory or steroid-dependent asthma
History of intubation and mechanical ventilation from a
previous asthma attack is the most powerful predictor of
the future severity of an asthma exacerbation.
464
III DISEASES
All that wheezes is not asthma; look for other life-threatening causes (Tables 3-5)
COMPLICATIONS
Acute Complications
Status Asthmaticus
Definitionsevere asthma attack, poorly responsive to
aggressive bronchodilator therapy, with a high probability
of progressing to respiratory failure
Table 3. Differential Diagnosis of Wheezing*

Upper airway obstruction
Extrathoracic
Intrathoracic
causes
causes
Postnasal drip
Gastroesophageal
reflux
Epiglottitis
Obesity
Vocal cord dysfunction or paralysis
Retropharyngeal
edema, abscess, or
hemorrhage
Irritant inhalants
Anaphylaxis
Factitious
Amyloidosis
Relapsing polychondritis
Cricoarytenoid
arthritis
Foreign body
aspiration
Tracheal stenosis
or tracheomalacia
Endobronchial
lesion
Intrathoracic goiter
Herpetic tracheobronchitis
Mediastinal tumor
or hemorrhage
Postpneumonectomy syndrome
Vascular compression from a rightsided aortic arch
or from a thoracic
aortic aneurysm
Local airway
obstruction
Asthma
COPD
Pulmonary edema
Pulmonary embolism
Pneumonia
Bronchiectasis
Cystic fibrosis
Adult respiratory
distress syndrome
Bronchiolitis obliterans
Bronchiolitis obliterans organizing
pneumonia
Eosinophilic infiltratration
Angioedema
Carcinoid syndrome
*Boldface, common conditions; italics, rare conditions and should be consid-
ered only after a standardized work-up fails to disclose an obvious cause.

Loeffler syndrome, eosinophilic pneumonia, polyarteritis nodosa, Churg-
Strauss syndrome, helminth infection, allergic bronchopulmonary

aspergillosis.
465
Work-upa clinical diagnosis (see above)

Treatmentis unchanged from that outlined below except
that most patients with status asthmaticus require endotracheal
intubation
Pneumothorax
Definitiona collection of gas within the pleural space with
or without shifting of the mediastinum (tension pneumothorax)
Work-up
Table 4. Some Historical Clues to the Cause of Wheezing

Historical clue
Scratchy throat, constant
throat clearing
Recent intubation
Wheezing during or immediately after a meal
Sore throat out of proportion
to exam findings
Paroxysmal nocturnal dyspnea,
orthopnea, acute weight gain
Connective tissue disease
Possible cause
Postnasal drip
Tracheal stenosis
Aspiration, foreign body, gastroesophageal reflux, anaphylaxis
Epiglottitis; retropharyngeal
edema, abscess, or hemorrhage
Congestive heart failure, cor
pulmonale from COPD
Bronchiolitis obliterans, bronchiolitis obliterans organizing
pneumonia, pulmonary fibrosis
Acute dyspnea (vs. insidious
Pulmonary embolism, aspiration,
onset)
foreign body, pneumothorax,
gastroesophageal reflux
Urticaria, hypotension, abdom- Anaphylaxis or angioedema
inal pain
Flushing with diarrhea
Carcinoid syndrome
Recurrent infections of upper Wegener granulomatosis, cystic
respiratory tract
fibrosis, bronchiectasis
Fevers
Pneumonia, bronchitis, malignancy, eosinophilic infiltration
Immunocompromised host
Herpetic tracheobronchitis
Young female with psychiatric Paroxysmal vocal cord motion
history with normal PFTs
(also called Munchausen
& radiographic findings
stridor)
Wheezing during exercise
Vocal cord dysfunction
Wheezing immediately after
Exercise-induced bronchospasm
exercise
PFT, pulmonary function test.
466
III DISEASES
Table 5. Physical Exam Pearls and Pitfalls Regarding
Wheezing Patients
Pearls
Pitfalls
Unilateral wheezing is pathologic Wheezing during expiration

and requires further investigation is characteristic of asthma
to exclude mechanical obstrucwhereas wheezing during
tion (such as endobronchial
inspiration is not (False)
lesions) (True)
The degree of wheezing
The use of accessory muscles
correlates with the degree of
(scalenes, sternocleiodomastoids, airway obstruction (False)
etc.); the presence of suprasternal or intercostal retractions; A patient who is not wheezing
the presence of paradoxical
does not have asthma
movement of the thorax and
(False)
abdomen (one rises while the
other falls); or the inability to
The absence of pulsus
lie flat is suggestive of severe
paradoxus excludes the
airway obstruction (True)
possibility of severe airway
obstruction (False)
The presence of digital clubbing
is not typical of asthmaeven The presence of hypoxia in a
severe asthmaand mandates a
person with asthma suggests
work-up for other diseases such
that asthma is the primary
as interstitial lung disease,
cause. (Falsehypoxia in
COPD, hypertrophic osteopathy,
particularly young asthma
etc. (True)
patients is a very late
finding; rarely in seniors or
The presence of a pulsus parathose with considerable
doxus of >10 mm Hg during
comorbidities will asthma
inspiration is seen in patients
prove to be the primary
with severe airway obstruction
cause of hypoxia)
(True)
An upright inspiratory posteroanterior chest X-ray can

detect a pneumothorax as small as 50 mL.
Supine chest X-rays require as much as 500 mL of air to
detect a pneumothorax.
Treatmenta thoracostomy tube is required for the following:
467
Pneumothorax >3 cm from the lateral wall to the edge of

the visceral pleura or
Pneumothorax >4 cm from the apex to the visceral pleura
A smaller pneumothorax in a nonventilated patient may be
treated with oxygen, thoracentesis, or observation.
Metabolic Complications
Monitor potassium (hyperkalemia from -agonist inhalers)
and glucose (hyperglycemia from corticosteroids).
Osteoporosis occurs with long courses of systemic (not
inhaled) corticosteroid therapy.
Chronic Complications
Progression to irreversible airway obstruction (COPD)
Decreased quality of life
Complications from long-term treatment with oral corticosteroids in patients with refractory asthma
When approaching a patient with suspected asthma always
Assess the severity of the patients respiratory status
Exclude alternative diagnoses
Confirm airway obstruction
Assessing Respiratory Status

The following signs suggest potential impending respiratory failure and should prompt intensive monitoring and consideration of mechanical ventilation:
Obtundation
Suprasternal or intercostal retractions
Weak respiratory effort
Paradoxical respiratory pattern (chest rises while abdomen
falls; chest falls while abdomen rises)
Respiratory rate >28 breaths/minute
Heart rate >130 beats/minute
Inability to lie flat
Arterial blood gases showing PaO2 60 mm Hg or PaCO2
40 mm Hg
Early in an asthma attack, tachypnea results in respiratory
alkalosis. The development of a normal PaCO2 suggests
impending respiratory failure.
468
III DISEASES
Pulsus paradoxus (Table 6)

Abnormal when >10 mm Hg
Associated with severe asthma
Excluding Alternative Diagnoses

Chest X-raymay show hyperinflation but is most helpful
to exclude other diseases
Bronchoscopysuspected foreign body aspiration, endobronchial lesions
Ventilation-perfusion scanningpulmonary embolism
Blood pressure
Table 6. How To Manually Calculate Pulsus Paradoxus

(PP)
ESBP
PP
ISBP
Inspiration
Expiration
The patient must be in sinus rhythm

Have the patient breathe normally throughout the procedure
Inflate a sphygmomanometer 30 mm Hg above the systolic blood
pressure
Slowly deflate the cuff until first Korotkoff sound is heard, then
stop deflating the cuff
Gently increase cuff pressure until the first Korotkoff sound is
heard intermittently. The pressure is the expiratory systolic blood
pressure (ESBP)
Now slowly deflate the cuff until the first Korotkoff sound is heard
regularly, then stop deflating the cuff. This pressure is the inspiratory systolic blood pressure (ISBP)
The pulsus is the difference between ISBP and ESBP
469
Computed tomography of the chestpulmonary embolism,

interstitial lung disease, mediastinal tumors
Serologic, sputum, or urine studieseosinophilic infiltration, Wegener granulomatosis, carcinoid syndrome, ChurgStrauss syndrome, eosinophilic bronchitis
Pulmonary function testsnot usually recommended in
acute exacerbations of asthma but full pulmonary function
tests are helpful in showing the following:
Flow loops suggestive of intrathoracic, extrathoracic, or
fixed airway obstruction
Impaired diffusion capacity of carbon monoxide suggesting interstitial lung disease
Presence of a restrictive process
Methacholine challengecontraindicated as a diagnostic
test during an exacerbation. It is helpful in outpatient workup when the diagnosis of asthma is questionable.
Consider occupational asthma.
Consider reactive airway dysfunction syndrome with history of acute inhalation injury.
Confirming Airway Obstruction

Peak Expiratory Flow (PEF)
PEF testing
Have the patient exhale as hard and fast as possible into the
peak flow meter. The final measurement is the average of
the best three readings. Compare this with the patients
known baseline.
Generally, patients having a severe exacerbation of
asthma
Have a PEF <120 L/minute or
Have a PEF <50% of known personal best PEF or of
standardized PEF or
Are too dyspneic to perform PEF assessments
Limitations of PEF testing
Correlation between PEF and FEV 1 has had limited
validation.
PEFs are better for excluding airway obstruction than for
confirming it.
A low PEF has a positive predictive value for a low FEV1
of 46.5% but a negative predictive value for a low FEV1
of 95%.
470
III DISEASES
PEF does not distinguish among causes of airway obstruction,

neuromuscular weakness, poor patient effort, and asthma.
MANAGEMENT
Goals
Relieve bronchospasm
Maintain oxygenation and ventilation
Suppress airway inflammation
Prevent subsequent exacerbations
Acute Management (Accepted Therapy)
Oxygen
Give oxygen nasally or by mask to maintain oxygen saturation >92%.
Objective measurement of ventilation (with arterial blood
gases) is critical to prevent delayed intubation of patients at
risk for respiratory failure (see above).
Albuterol
Metered dose inhaler, 4-6 puffs every 20 minutes, or nebulizers, 2.5-5.0 mg every 20 minutes, until relief or onset of
side effects (tachyarrhythmias or severe tremors)
No difference in clinical response between nebulizers and
metered dose inhalers with spacers in acute exacerbations
of asthma, but nebulizers are associated with a high frequency of tachyarrhythmias.
Continuous albuterol administration via a nebulizer (10
mg/hour) has been advocated in severe cases.
Corticosteroids
Methylprednisolone, 125 mg IV, followed by 40-60 mg every
6 hours for 24-48 hours, then switch to prednisone, 60 mg PO
Corticosteroid tapers are not necessary if corticosteroids are
used for <10 days.
Corticosteroid use reduces relapses after hospitalization or
emergency department presentation, rapidly improves airway obstruction (by FEV1), and possibly reduces the likelihood of death from asthma.
471
Ipratropium
Metered dose inhaler, 4-8 puffs every 30 minutes, or nebulizer, 0.5 mg every 30 minutes
Increases bronchodilation when given with albuterol
No evidence for role in asthma exacerbation
Other Agents
Long-acting 2-agonists (salmeterol) do not provide relief
during acute attacks, but they should not be discontinued at
the hospital if they were being used before admission.
Epinephrine (SQ or IV) has not been shown to be as effective as inhaled 2-agonists and is not recommended.
Aminophylline has not shown benefit and is not routinely
recommended.
Magnesium IV has not shown important benefit in asthma and
is not routinely recommended.
Role of anti-IgE therapy with omalizumab in acute exacerbations is undefined.
Interventions With Unproven Benefit and Potential Harm

Mucolytics
Antibiotics (unless in the setting of infection)
Chest physiotherapy
Aggressive hydration
Chronic Management
Mild Intermittent Asthma
Inhaled short-acting -agonists as needed
2
Mild Persistent Asthma
One of the following:
Low-dose daily inhaled corticosteroids
Cromolyn
Methylxanthine (e.g., theophylline or aminophylline)
Antileukotrienes (e.g., zileuton or zafirlukast)
Moderate Persistent Asthma

Medium dose daily inhaled corticosteroids and
Long-acting inhaled -agonists (e.g., salmeterol)
2
472
III DISEASES
Severe Persistent Asthma
High-dose daily inhaled corticosteroids and
Long-acting inhaled -agonists and
2
Systemic corticosteroids
Developing a Long-Term Asthma Plan
Developing an outpatient plan for patients with asthma is
beyond the scope of this chapter, but its importance cannot
be overstated.
473
III DISEASES
ATRIAL FIBRILLATION
Garvan C. Kane, M.D.
Arshad Jahangir, M.D.
DEFINITION
Atrial fibrillation (AF)
Irregular, disorganized electrical activity of the atria with
an irregular ventricular response
On ECG, P waves are absent and irregular waveforms
continuously change in shape, duration, amplitude, and
direction.
CLASSIFICATION
ParoxysmalEpisodes terminate spontaneously, recur, and
last <48 hours.
PersistentContinuous AF that can be converted to sinus
rhythm
PermanentOngoing AF refractory to reversion or allowed
to continue
ETIOLOGY
Commonischemic heart disease, dilated cardiomyopathy,
familial, chronic hypertension, valvular disease (particularly
rheumatic mitral stenosis), advanced age, postcardiac surgery
Other cardiac predictorspresence of left atrial enlargement, left ventricular hypertrophy, ventricular dysfunction,
acute myocardial infarction (10% of persons with acute
myocardial infarction have an associated episode of AF and
up to 20% if they develop congestive heart failure), sinus
node dysfunction, hypertrophic cardiomyopathy, WolffParkinson-White syndrome
Noncardiac precipitatorshyperthyroidism, alcohol (holiday
heart syndrome), severe infection, pulmonary embolism
Special abbreviation used in this chapter: AF, atrial fibrillation.

475
Lone AFAF in the absence of recognizable heart disease

or precipitating illnesses
Note: Every patient who presents only with acute onset of
AF does not need to be ruled out for a myocardial infarction
or screened for an occult pulmonary embolus. Although
AF may be associated with these conditions, it is quite uncommon in the absence of other clinical clues (symptoms, ECG
changes, hypoxia)
EPIDEMIOLOGY
AF affects 2.3 million Americans and results in 75,000 strokes
annually.
The incidence of AF is estimated at 0.4% of the general population and increases with age: 2%-5% at age 65 and 9% by
age 80.
Prevalence of paroxysmal AF is 22%-65%, about one-fourth
of cases will progress to persistent form.
Presence of valvular heart disease, left atrial or left ventricular enlargement, left ventricular hypertrophy, or ventricular
systolic dysfunction increases the risk of progression to permanent AF.
Many patients may be asymptomatic or complain of malaise
or palpitations.
The elderly or those with compromised coronary or cerebral circulation may present with dizziness or angina.
Heart failure may occur because of rapid rates or loss of atrial contribution to ventricular filling.
Thromboembolic stroke often can be the first presentation of
AF (1 of every 6 strokes occurs in patients with AF).
Some patients complain of episodic polyuria, probably
secondary to increased production of atrial natriuretic peptide.
Clinical Signs of AF
Irregularly irregular rhythm with variable intensity of the
first heart sound
No a wave in the jugular venous pressure and no fourth
heart sound
476
III DISEASES
Absent presystolic accentuation of mitral stenosis murmur

Pulse varies in amplitude because of differing diastolic filling times.
The apical rate exceeds the radial rate (pulse deficit).
Signs of Complications
What is the degree of patient distress?
Presence or absence of chest pain or altered level of consciousness?
Check blood pressure yourself.
Signs of congestive heart failure (increased jugular venous
pressure, third heart sound, pulmonary crackles)
ECG Clues
Absent P waves, fibrillatory waves may be seen (especially
in V1, V2).
Irregularly irregular, normal-looking QRS complexes; aberrant ventricular conduction (wide QRS) of atrial impulses
may be present, usually with long-short cycle (Ashman phenomenon) or with very rapid rates.
Watch for presence of delta waves on ECG (if irregular wide
QRS complexes with varying duration).
Investigations
CBC, electrolytes, magnesium, sTSH, chest X-ray
CK-MB, troponin T (depending on history)
PATIENT WITH UNSTABLE AF

Signs and plan of action are indicated in Figure 1.
FIVE-STEP MANAGEMENT OF PATIENTS WITH AF

Step 1Treat Underlying Cause
Rule out ischemia, hypoxia (pulmonary embolism), congestive heart failure, or other primary conditions such as
hyperthyroidism, myocarditis, acute pulmonary decompensation.
AF reverts spontaneously to normal sinus rhythm in 68% of
patients within 72 hours.
477
478
Signs of unstable AF
Chest pain
SBP <100 mm Hg
Severe dyspnea or CHF
Syncope/presyncope
Clouding of consciousness
Plan immediate synchronized

DC cardioversion
Call senior resident

Place patient on cardiac monitor
Place defibrillator pads on patient
Oxygen at 6-10 L/minute
Peripheral IV access with some IV fluid running
If patient awake, needs sedation (e.g., midazolam 2-5 mg IV)
Designate primary control of patient's airway to responsible person
Cardiovert starting a 70 J (biphasic) or 200 J (monophasic)
synchronized to QRS complexes
Fig. 1. Signs of instability and plan of action. AF,

atrial fibrillation; CHF, congestive heart failure;
SBP, systolic blood pressure.
III DISEASES
Step 2Control Ventricular Rate
The fast ventricular response rate is the cause of predominant
symptoms in patients with AF and even within a few weeks
can result in a tachycardia-induced cardiomyopathy.
If the patient is stable but the heart rate is >150 beats/minute,
use IV medications for rate control in a monitored setting
(Table 1).
Aim for a ventricular rate <80 beats/minute at rest and <120
beats/minute with activity.
Calcium Channel Blockers
Caveats
Avoid in severe left ventricular dysfunction or WolffParkinson-White syndrome.
Table 1. Drugs for Controlling Ventricular Rate

Drug
Metoprolol
Propranolol
Esmolol
Diltiazem
Verapamil
Digoxin
Loading dose
Maintenance dose
5 mg IV push every
5 minutes 3
5-10 mg IV every 6 hours

or 25-100 mg PO every
12 hours
0.5-1 mg IV push every Propranolol LA 60-320
5 minutes to maximum mg PO daily
of 6 mg (0.1 mg/kg)
500 g/kg (over 1
50-300 g/kg per minute
minute)
IV
0.25 mg/kg over 2
IV 5-15 mg/hour
minutes (10-20 mg)
90-240 mg/day PO
followed by 0.35
mg/kg over 5 minutes
if needed
5-10 mg IV over 2
120-360 mg daily
minutes, repeat in 10
minutes, then 0.005
mg/kg per minute for
30-60 minutes
1 mg over 24 hours in
0.125-0.5 mg IV or PO
3-4 divided doses
daily
LA, long acting.

479
Diltiazem usually is well tolerated and can be administered in an infusion that is easily titrated to effect. It has
replaced digoxin as a first-line agent for patients with a normal ejection fraction.
Diltiazem PO is a good alternative to IV, with an onset of
action at 30 minutes.
-Blockers
Best choice in high catecholamine states (ischemia,
postoperatively)
Caveats
Avoid in severe left ventricular dysfunction, moderate to
severe asthma, or Wolff-Parkinson-White syndrome.
Use cautiously in patients with COPD.
-Blockers are safe for diabetic patients except for a small
number who are insulin-dependent and have poor hypoglycemic awareness.
There is no evidence for avoiding -blockers in patients
with peripheral vascular disease.
Esmolol is safer than other -blockers because of a shorter half-life (10 minutes); it is ineffective without a bolus
and is expensive.
Digoxin
This traditionally has been the first-line agent.
Caveats
Avoid in Wolff-Parkinson-White syndrome.
First choice for severe left ventricular dysfunction or aortic stenosis
Compared with drugs mentioned above, digoxin has less
efficacy, slower onset of action, and more side effects
(heart block, ventricular dysrhythmias, nausea and vomiting, yellow-green visual hallucinations).
It is ineffective at slowing heart rate in the setting of
increased sympathetic tone (e.g., hyperthyroidism,
fever, hypoxia, hypovolemia, exercise, or other form of
stress).
Often good as an adjunct to -blockers or calcium channel blockers
Reduce dose in the elderly and those with renal impairment.
Ideally, the dose should be withheld before cardioversion.
480
III DISEASES
Dose needs to be reduced by half if propafenone, amiodarone, or quinidine is added for rhythm control.
Clonidine
Decreases sympathetic tone
Not widely used
Give 0.075 mg PO and repeat in 2 hours if no important effect
Step 3Convert to Normal Sinus Rhythm

An attempt to restore sinus rhythm should be considered for
all patients with AF.
Longer duration of AF (particularly >3 years) and certain
causes, such as those associated with a dilated left atrium
(>60 mm), make successful cardioversion or maintenance
of sinus rhythm unlikely.
Calcium channel blockers, digoxin, and -blockers usually
do not cause reversion to normal sinus rhythm.
Electrical cardioversion is effective 80% (monophasic) and
up to 95% (biphasic) of the time and pharmacologic cardioversion, 40%-80%.
Elective Electrical Cardioversion

Patient should be fasting for 6 hours.
Withhold preceding digoxin dose, and make sure potassium and magnesium levels are normal.
Monophasic defibrillatorstart at 200 J, 300 J, 360 J
Biphasic defibrillator70 J, 120 J, 150 J
If unsuccessful, infuse ibutilide and then cardioversion
Pharmacologic Cardioversion
Include IV procainamide or ibutilide (avoid ibutilide in
patients with severe systolic dysfunction or prolonged QT
intervals; 3% develop torsades de pointes after receiving
ibutilide).
Oral options include sotalol (only proven effective in AF
after open-heart surgery), flecainide, propafenone, quinidine, dofetilide (characteristics similar to IV ibutilide).
In patients with tachycardia-bradycardia syndrome, long
481
pauses could be observed after cardioversion before resumption of normal sinus rhythm.
Step 4Maintain Sinus Rhythm
Recurrence 50%-75% of the time
Antiarrhythmic agents maintain sinus rhythm in up to
50%-65% of patients at 1 year.
However, these agents could cause life-threatening ventricular tachycardia or fibrillation in 2%-3.5% of patients
with normal hearts and up to 15% of those with a history
of ventricular dysfunction or arrhythmias.
All patients with structurally abnormal hearts are monitored
in hospital until they have had 5 doses of the drug (5 halflives). For amiodarone, the loading dose is generally 5-6 g
(600 mg twice daily).
With the use of class III (sotalol, dofetilide, ibutilide) or
class IA (quinidine, procainamide, disopyramide) antiarrhythmics, QTc duration needs to be monitored, as does the
QRS duration with class IC antiarrhythmics.
Sotalol and amiodarone because of the additional antiadrenergic effect have the added advantage of slowing the
ventricular response when AF occurs.
Maintaining sinus rhythm in high-risk patients with AF with
the use of antiarrhythmic agents does not improve survival
compared with those treated for rate control alone. The rate
control approach resulted in fewer complications (AFFIRM
trial) in high-risk AF patients.
Maze procedure
Surgical technique resulting in up to 90% success of maintaining normal sinus rhythm
However, up to 2% of patients need pacemakers.
A variety of percutaneous catheter-based procedures are
available, including ablation for pulmonary vein isolation
or atrioventricular node (with pacemaker insertion for rate
control)
Step 5Prevent Embolic Complications

Anticoagulation for Chronic AF
AF causes 14% of all strokes in patients older than 60 years.
The risk of stroke for patients with AF is highest during the
first few months after onset of the arrhythmia.
482
III DISEASES
Risk factors for thromboembolic events in AF

Risk factors are listed in Table 2.
Risk of embolization per year is given in Table 3.
Recommendations for anticoagulation are outlined in Table 4.
Anticoagulation for Acute AF

If patient has been in AF for 48 hours, the risk of pericardioversion embolization is 5.5%.
This is reduced to 1% if the patient is anticoagulated, with
therapeutic INR (2-3) for at least 3 weeks before and 4 weeks
after cardioversion.
Table 2. Risk Factors for Thromboembolic Events in

Atrial Fibrillation
History of previous emboli
Hypertension
History of congestive heart failure
Age >75 years
Diabetes mellitus
Left ventricular ejection fraction <0.40
Left atrial size >2.5 cm/m2
Table 3. Risk of Embolization Per Year

No. of risk factors
Risk, %
0
1 or 2
3 or more
1
5-6
8-19
Table 4. Recommendations for Anticoagulation*

Age, years
<65
65-75
>75
No risk factors
Aspirin 325 mg daily/no therapy
Aspirin/warfarin
Warfarin
>1 risk factor

Warfarin
*Note: Warfarin to goal INR 2-3 (INR <1.8 offers no protection).

483
Alternatively, transesophageal echocardiography stratifies

patients with AF according to embolization risk.
No evidence of atrial thrombus or spontaneous echogenic
smokeCardiovert with IV heparin and warfarin for 4
weeks, with therapeutic INR (2-3).
Atrial stunningDelayed onset of effective atrial contractions after normal electrical activity has been reestablished may increase thrombogenic potential. Thus, 4
weeks of anticoagulation after cardioversion is indicated.
Stunning occurs with both electrical and pharmacologic
cardioversion.
484
III DISEASES
CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
DEFINITIONS
American Thoracic Societys official statement on COPD:
COPDa disease state characterized by airflow obstruction due to chronic bronchitis or emphysema, which is
generally progressive, may be accompanied by airway
hyperreactivity, and may be partially reversible
Chronic bronchitisthe presence of chronic productive
cough for 3 months in each of two successive years in a
patient in whom other causes of chronic cough have been
excluded. Definition is clinical.
Emphysemaabnormal permanent enlargement of the
airspaces distal to the terminal bronchioles, accompanied
by destruction of their walls and without obvious fibrosis.
Destruction is defined as lack of uniformity in the pattern of respiratory airspace enlargement; the orderly
appearance of this acinus and its components is disturbed
and may be lost. Definition is pathologic.
COPD exacerbationacute flare or worsening of chronic COPD symptoms; not attributable to other confounding
conditions (pneumonia, congestive heart failure) with
demonstrable decline in pulmonary function. Triggered by
various stimuli, including infections and environmental
exposures. More frequent in patients with comorbid
conditions.
Cardinal features
- Worsening dyspnea
- Increased sputum purulence
- Increased sputum volume
Classification
The classification of COPD is given in Table 1.
485
Table 1. Classification of COPD

Classification*
Emphysema
Chronic
bronchitis
Diagnosis is based on
Pathologic demonstration of destruction of
alveolar architecture
Clinical features, including productive
cough
Overlap is common;
often best to designate
as predominantly
emphysema
or bronchitis
*The distinction between emphysema and chronic bronchitis is somewhat
arbitrary and has little clinical value.
ETIOLOGY
Smoking tobacco in at least 85%-90% of patients
Others: -antitrypsin deficiency, environmental (second1
hand) tobacco smoke, occupational and environmental
exposures
Airway hyperresponsiveness may be a predisposing factor.
Infections are the most common identifiable cause of acute
exacerbations.
The most common organisms implicated are Haemophilus
influenzae, Streptococcus pneumoniae, Moraxella
catarrhalis, Mycoplasma pneumoniae, influenza virus,
and adenovirus (Table 2).
EPIDEMIOLOGY
In the U.S., 16 million people have COPD.
COPD is the fourth leading cause of death, after heart disease,
cancer, and stroke.
Prevalence and mortality of COPD are increasing, especially among women.
The majority of patients with COPD are long-time smokers.
Symptoms usually appear in the fifth or sixth decade.
Patients with an acute exacerbation present with (usually)
the following:
Known underlying COPD
One or more of three cardinal characteristics:
Worsening dyspnea
486
III DISEASES
Increased sputum purulence

Increased sputum volume
Often one or more identifiable trigger(s)
Complications
The most common causes of death of persons with COPD
are cardiovascular disease and lung cancer.
The major complication of a COPD exacerbation is respiratory failure.
Table 2. Triggers for COPD Exacerbation

Bacterial respiratory tract infection or colonization
Haemophilus influenzae
Pseudomonas aeruginosa
Streptococcus pneumoniae
Moraxella catarrhalis
Mycoplasma pneumoniae
Chlamydia pneumoniae
Viral respiratory tract infection
Rhinovirus
Adenovirus
Influenza virus
Other viruses
Environmental exposures
Particulate pollutants (<10 m, especially <2 m)
Ozone
Nitrogen dioxide
Sulfur dioxide
Exacerbations of comorbid conditions
Heart failure
Nonpulmonary infections
Pulmonary thromboembolism
Bronchospasm
Pneumothorax (often secondary to underlying COPD)
Iatrogenic
Excessive sedation from medication
Anesthesia, especially with prolonged surgery of thorax or
upper abdomen
Electrolyte disturbances causing decreased ventilatory drive
Unexplained (a large proportion of cases)
487
Clinical measures to follow include respiratory rate, use of

accessory muscles, evidence of respiratory distress, paradoxical breathing, oxygen saturation determined with
pulse oximetry, and evidence of hypoxia or hypercapnia
as determined with arterial blood gases.
EVALUATION
The initial evaluation is outlined in Table 3.
Relevant lab and imaging tests are listed in Table 4.
Chronic COPD
The diagnosis of advanced COPD suspected clinically,
based on historical and physical findings at the time of
evaluation.
The likelihood of advanced COPD in a patient who is or
has been a smoker and who has consistent symptoms and
signs is extremely high.
Assessment of severitySpirometry is mandatory for
staging severity (Table 5)
MANAGEMENT OF ACUTE EXACERBATIONS

General Measures
See Table 3
Decide whether the patients condition warrants hospital
stay (Table 6) or admission to the ICU (Table 7).
The goals of treatment for COPD exacerbation are
To remove any ongoing triggers
To restore the patients baseline work of breathing through
aggressive supportive measures
Many therapies are empiric. Of these, many have data to
support their use (Table 8).
Consult a pulmonary specialist when COPD exacerbation
is complicated with any of the following:
Hemoptysis
Pneumothorax
Severe pneumonia
Respiratory failure requiring mechanical ventilation
Anatomic airway obstruction
Undefined lung disease
Large or recurrent pleural effusion
488
III DISEASES
PROPHYLAXIS
Therapeutic considerations for the time of hospital discharge,
including guidelines for home oxygen therapy, are outlined
in Tables 8 and 9.
Table 3. Initial Evaluation of Patients With Suspected
COPD Exacerbation
History
Smoking history (past & current, amount)
Environmental & occupational exposures
Residence in or travel to heavily polluted areas
Exposure to environmental (second-hand) tobacco smoke
Acute & chronic pulmonary illnesses
Cough
Daily cough & sputum production 3 months out of each
of 2 successive years defines chronic bronchitis
Wheezing
Dyspnea (note severity & any change from baseline)
Physical exam
Signs of hyperinflation (severe emphysema)
Increased anteroposterior diameter
Low diaphragmatic position
Faint breath & heart sounds
Inspiratory retraction of lower ribs from flattened
diaphragm (Hoover sign)
Signs of obstruction
Prolonged expiratory phase of respiration
Wheezing
Pursed-lip breathing
Hypertrophy of scalene muscles
Signs of cor pulmonale (pulmonary hypertension in setting of
lung disease)
Increased jugular venous pressure
Right ventricular heave
Third/fourth heart sound or prominent pulmonic second
sound, tricuspid regurgitation murmur (sign of advanced
disease)
Edema, hepatomegaly
Plethora or cyanosis (clubbing not associated with COPD
think of cystic fibrosis, lung cancer, interstitial pulmonary
fibrosis, asbestosis)
489
Table 4. Lab and Imaging Tests

Blood & sputum cultures, Gram stain (include Legionella and atypical organisms)
CBC & electrolytes
Chest X-raymay show hyperinflation, oligemia, & bullae; helps
rule out other lung disease
Peak flow measurementshelp to quantify bronchospasm & follow
condition objectively
Arterial blood gasesimportant in severe exacerbations to identify
hypoxic (PaO2 <60 mm Hg) or hypercapnic (>50 mm Hg, with pH
<7.35) respiratory failure
Table 5. Staging of COPD*

Stage
Mild (at risk)
Moderate
Severe
Very severe
Features
FEV1/FVC >0.7, FEV1 80% predicted
Minimal symptoms with normal or nearnormal exam
FEV1 50%-80% predicted
Cough with or without sputum
Dyspnea on exertion
May have wheezing
FEV1 30%-50% predicted
Prominent cough
Dyspnea on exertion or at rest, hyperinflation,
wheezing, cyanosis, edema
FEV1 <30% predicted
FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.

*Not at time of acute exacerbation.
490
III DISEASES
Table 6. Criteria for Hospital Admission for COPD
Exacerbation
Progressive symptoms leading to concern of impending respiratory
failure
Failure of outpatient management, with worsening symptoms
and/or respiratory lab values
Difficulty with activities of daily life, eating, or sleeping because of
dyspnea
Coexisting pulmonary or respiratory muscle disease with limited
respiratory reserve
Worsening hypoxia or acute respiratory acidosis
Cor pulmonale with evidence of worsening right-heart failure
Coexisting respiratory depression
Intoxication
Excess sedation from analgesics or other psychotropic
medications
Need for procedure requiring anesthesia
Patient support not available for required home care
Table 7. Criteria for ICU Admission for COPD

Exacerbation
Need for intubation or noninvasive positive pressure ventilation
Respiratory muscle fatigue or respiratory failure
Hypoxia
Uncompensated respiratory acidosis
Inability to protect & maintain airway integrity
Poor response to initial therapies
Persistent, severe dyspnea
Worsening respiratory lab values despite treatment
Persistent mental status changes due to respiratory failure
491
Table 8. Therapies for COPD Exacerbation, With

Strength of Supporting Evidence
Therapy
Result and dose
Supported by randomized, controlled clinical trials

Oral corticosteroids Outcomesshorter length of hospital stay,
lower rates of treatment failure & repeat
hospitalization
Usual dose: prednisolone 25-125 mg IV/PO
2-4 times daily initially, then tapered over
14 days (longer taper not beneficial)
Inhaled anticholiner- Ipratropium showed significant FEV1
gic drugs
improvement vs. placebo (effect size not
calculable)
Tiotropium 18 g daily (long-acting anticholinergic) improved FEV1 significantly
better than placebo, slightly better than
ipratropium
Inhaled 2-agonist
More variable response than with antidrugs
cholinergics; may depend on degree of
airway hyperresponsiveness
Significant improvement in FEV1 and/or
symptoms in up to 50% of patients vs.
placebo
No difference in outcome between nebulized
& metered dose inhaler preparations;
correct inhaler technique critical
Combination of
Significant improvement in FEV1 in most
anticholinergic
patients, compared with either drug alone
& 2-agonist
drugs
Supported by some evidence from poor studies;
not proven; benefits probably outweigh risks
Antibiotics
Accelerated improvement in FEV1 & lower
relapse rates
Positive Gram stain & culture results not
necessarystart empiric therapy with
trimethoprim-sulfamethoxazole, doxycycline, or a quinolone with strep coverage
(levofloxacin, gatifloxacin, etc.) for 10 days
Supported by some evidence; usefulness
limited because of adverse effects
Theophylline
Variable improvement in FEV1 from 0%-20%
Narrow therapeutic range; common adverse
effects even in therapeutic range: nausea,
diarrhea, headache, seizures, arrhythmia
492
III DISEASES
Table 8 (continued)
Therapy
Inhaled corticosteroids
Mucolytics (Nacetylcysteine,
iodides)
Chest physiotherapy
Cilomilast (nontheophylline
phosphodiesterase-4 antagonist)
Zanamivir
Anabolic steroids
(androgens)
Result and dose

No evidence of benefit
No benefit in acute exacerbation
Little evidence of benefit
May worsen bronchospasm
Extrapolated from evidence in cystic fibrosis
literature
Little benefit in COPD exacerbation
May worsen bronchospasm
Experimental therapies
Currently in phase III trials; improved FEV1
& fewer exacerbations in some trials
Faster resolution of influenza symptoms &

fewer complications in some trials
No effect on pulmonary function
Rare case reports of causing exacerbations
of asthma & COPD
Speculative, no published studies
Prohibitive adverse effects in women
FEV1, forced expiratory volume in 1 second.
493
Table 9. Strategies for COPD Maintenance After

Stabilization of Acute Exacerbation
Therapy
Comment
Accepted as standard of care; some evidence

to support recommendation
Establish diagnosis Wait until acute episode resolves to assess
& stage (severity)
baseline lung function & assign to a stage
of disease
Encourage lifestyle Critical to slow progression of disease &
changes
reduce exacerbations
Reduce adverse exposures, including
Smoking cessa- Help patient move through stages of cessation
tion: precontemplation, contemplation,
preparation, action, maintenance. Use encouragement, continued social support systems, nicotine replacement, bupropion, etc.
Immunizations
Pneumococcal and influenza vaccines
Exercise
Improves quality of life; fewer hospitalizations; no effect on FEV1
Inhaled antichoBetter than either drug alone; bronchodilation and symptomatic improvement; does
linergic/2-agonist
combination
not improve survival
Home oxygen ther- Improves survival of patients with
apy if indicated
hypoxemia
(Table 10)
Lung volume
Offered at certain centers as result of the
reduction surgery
National Emphysema Treatment Trial;
beneficial only for some patients
Evidence equivocal; recommendations debated
Inhaled corticoSome studies suggest fewer exacerbations &
steroids
readmissions; improvement in lung function
is small, early, and noncumulative; systemic
adverse effects occur
Theophylline
Trade-off between benefit and harm; small
improvement in lung function, but frequent
adverse effects
Mucolytic agents
Showed decreased number of exacerbations
& modest improvement in lung function
No evidence to support recommendation
Antibiotics
No well-designed studies; no clear indication
for long-term use
Oral corticosteroids Only 20%-30% of patients have short-term
response; no evidence of slowed progression of disease, multiple adverse effects
494
III DISEASES
Table 10. Oxygen Therapy After Hospital Discharge of
Patients With COPD Exacerbation
PaO2
SaO2 or SpO2
<55 mm Hg
55-59 mm Hg
<88%
88%
60 mm Hg
88%
O2 indicated
Yes
If cor pulmonale, erythrocytosis, or
congestive heart failure
If documented nocturnal hypoxia
despite CPAP or coexisting severe
lung disease
CPAP, continuous positive airway pressure; SaO2, arterial oxygen saturation;

SpO2, oxygen saturation determined by pulse oximetry.
495
III DISEASES
CONGESTIVE HEART FAILURE
DEFINITIONS
Congestive heart failure is a clinical syndrome characterized by
Impairment of cardiac contraction or relaxation or both
Increased left ventricular end-diastolic pressure (frequently
measured by its surrogate, pulmonary capillary wedge
pressure) >18 mm Hg
Neurohormonal activation, fluid retention, pulmonary
congestion, decreased exercise tolerance, and reduced
survival
Systolic dysfunction
Decreased left ventricular ejection fraction
Asymptomatic or detected incidentally
Classic signs and symptoms of heart failure
Diastolic dysfunction (stiff ventricle)
Increased resistance to ventricular filling resulting in
increased left ventricular filling pressures
May result in congestive symptoms in the absence of systolic dysfunction
DIAGNOSIS AND TYPES
The criteria for diagnosing congestive heart failure are listed
in Table 1.
The types of congestive heart failure are compared in
Table 2.
Acute and chronic congestive heart failure are compared in
Table 3.
Special abbreviations used in this chapter: ACE, angiotensin-converting enzyme;

ARB, angiotensin II receptor blocker; S3, third heart sound; S4, fourth heart
sound.
497
Table 1. Framingham Criteria for Diagnosis of

Congestive Heart Failure*
Major criteria
Paroxysmal nocturnal dyspnea or orthopnea
Neck vein distension
Rales
Cardiomegaly
Acute pulmonary edema
S3 gallop
Increased venous pressure >16 cm H2O
Circulation time >25 seconds
Hepatojugular reflux
Minor criteria
Ankle edema
Night cough
Dyspnea on exertion
Hepatomegaly
Pleural effusion
Vital capacity decrease 1/3 from maximum
Tachycardia (rate >120 beats/minute)
Major or minor criterion
Weight loss >4.5 kg in 5 days in response to treatment
S3, third heart sound.
*Diagnosis requires 2 major or 1 major and 2 minor criteria.
ETIOLOGY
Systolic Dysfunction
Ischemic cardiomyopathy (60% of patients)myocardial
infarction, unstable angina, left ventricular aneurysm, hibernating myocardium, myocardial stunning
Dilated cardiomyopathies (18% of patients)alcohol-induced,
viral, idiopathic, peripartum, tachycardia-induced, drugs
(Table 4)
Advanced valvular heart disease (12%)mitral regurgitation,
aortic regurgitation, aortic stenosis
Congenitalatrial septal defect, ventricular septal defect
Hypertensive heart disease (<10% of patients)
Sepsis and systemic inflammatory response syndrome
Inflammatory diseasessystemic lupus erythematosus,
Endocrine disordershyperthyroidism, hypothyroidism,
acromegaly
Genetic diseaseDuchenne and other muscular dystrophies
498
Table 2. Comparison of Types of Congestive Heart Failure

Symptoms
DOE, PND, OR
S3, HJR, rales
Signs
Ejection fraction
Right-sided
DOE, weight
Low output
High output
Systolic
Diastolic
DOE, weight
DOE
DOE, PND, OR
DOE, PND
Right ventricular lift,

liver enzymes,
edema
Congestive signs
S3, pulse pressure
Congestive signs
S4, sustained PMI
Causes
CAD, myocarditis, HTN, valve disease,
congenital
MS, left ventricular failure, PHTN
CAD, valvular, myocarditis

T4, AR, beriberi, Paget disease
CAD, myocarditis, valvular
Acute myocardial infarction, HTN crisis,
amyloidosis, hemochromatosis
AR, aortic regurgitation; CAD, coronary artery disease; DOE, dyspnea on exertion; HJR, hepatojugular reflux; HTN, hypertension; MS, mitral
stenosis; OR, orthopnea; PHTN, portal hypertension; PMI, point of maximum impulse (apex); PND, paroxysmal nocturnal dyspnea; S3, third
heart sound; S4, fourth heart sound; T4, thyroxine.
499
III DISEASES
Type
Left-sided
Table 3. Comparison of Acute and Chronic Congestive

Heart Failure
Decompensated Compensated
chronic
chronic
Feature
Acute
Symptom severity
Pulmonary edema
Peripheral edema
Weight gain
Whole-body fluid
load
Cardiomegaly
++++
++++
++++
++++
++++
++++
++++
++/+++
+
+++
+++
++++
++++
++++
Table 4. Drugs Associated With Cardiomyopathy

AntibioticsAZT (zidovudine), chloroquine, ddI (didanosine)
Antipsychoticslithium, phenothiazines
Antineoplasticsbleomycin, busulfan, cisplatin, doxorubicin,
methotrexate, vincristine
Othersalcohol, cocaine
Diastolic Dysfunction
Myocardial ischemiaoccurs earlier than systolic dysfunction
Hypertension
Valvular diseasesaortic stenosis
Primary restrictive cardiomyopathiesidiopathic, endomyocardial fibrosis, eosinophilic (Lffler endocarditis)
Secondary restrictive cardiomyopathiesamyloidosis,
hemochromatosis, Gaucher disease, Hurler syndrome,
sarcoidosis
Hypertrophic obstructive cardiomyopathy
High-Output Failure
Anemia
Hyperthyroidism
Thiamine deficiency (beriberi)
Arteriovenous fistulas
Paget disease
Multiple myeloma
Pregnancy
500
III DISEASES
Isolated Right-Heart Failure
Congenitalisolated secundum atrial septal defect, sinus
venosus atrial septal defect, pulmonary stenosis, Ebstein
anomaly
Right ventricular infarctionassociated with 1/3 of inferior myocardial infarctions
Cor pulmonale
Pulmonary hypertensionprimary, chronic thromboembolic
disease, mitral regurgitation
Arrhythmogenic right ventricular dysplasia
Uhl anomaly
EPIDEMIOLOGY
Framingham Heart Study estimates of prevalence of heart
failure:
Age 50-598/1,000 men, 8/1,000 women
Age 80-8966/1,000 men, 79/1,000 women
Higher prevalence for African Americans
These values likely represent underestimates because
Framingham Heart Study included only symptomatic cases
of systolic or diastolic dysfunction based on exam, chest
X-rays, ECGs.
After establishing the clinical diagnosis of congestive heart
failure, always look for a treatable cause (Table 5).
History
Dyspnea on exertion is earliest and most constant symptom
in all forms of heart failure.
Orthopnea and paroxysmal nocturnal dyspnea occur later
and tend to disappear after the right ventricle fails.
Weakness, fatigue, edema, and weight gain (most often in legs
and abdomen)
Look for precipitating factors
Dietary salt loadmost common factor but is diagnosis of
exclusion
Medication noncompliancesecond most common factor
501
Table 5. Treatable Causes of Congestive Heart Failure

Surgical treatment
Coronary artery diseasebetter myocardial perfusion may
occasionally improve congestive heart failure
Valvular diseasemitral regurgitation, aortic regurgitation,
mitral stenosis, aortic stenosis
Atrial septal defect
Left atrial myxoma
Arteriovenous fistulas
Medical cure
Thyrotoxicosis
Acromegaly
Beriberi
(lack of diuretics or excess digitalis; use of other drugs, e.g.,

NSAIDs; negative inotropics; alcohol)
Infectionviral, pneumonia, urinary tract, skin, sinus
Ischemiaalways needs to be ruled out
ArrhythmiaAnything other than sinus rhythm may
decompensate congestive heart failure (15%-20% of
patients with congestive heart failure have atrial
fibrillation).
Other organ dysfunctionrenal insufficiency, hypothyroidism, hyperthyroidism, anemia, COPD
Pericardial disease
Hypertension
Physical Exam
Classic signs of systolic heart failurebilateral basal lung
rales (crackles), third heart sound (S3), lower extremity or
sacral edema, elevated jugular venous pressure
A right-sided S increases with respiration.
3
A loud fourth heart sound (S ) may indicate a diastolic cause.
4
A prominent v wave is found in tricuspid regurgitation.
Hepatojugular reflux in the absence of other signs of congestive heart failure may be an early sign of a fixed stroke volume and asymptomatic left ventricular dysfunction (more
commonly, occurs in association with florid congestive heart
failure when pulmonary wedge pressure is >18 mm H2O).
502
III DISEASES
A sustained left ventricular impulse suggests left ventricular

hypertrophy and a diastolic cause.
Bounding carotid pulses suggest aortic regurgitation, thyrotoxicosis, arteriovenous fistula, or beriberi as cause of failure.
A prominent right ventricular lift suggests cor pulmonale,
pulmonary hypertension, thromboembolic disease, or mitral
regurgitation as cause of failure.
A systolic murmur that increases with the Valsalva maneuver suggests hypertrophic obstructive cardiomyopathy.
Although rare, ascites can present without pronounced peripheral edema.
DIAGNOSTIC STRATEGY
ECG
Rate
In florid congestive heart failure, usually tachycardia,
more worrisome if bradycardia
Rhythm
Look for rhythms that need to be cardioverted or paced.
Ischemia
Inverted T wave
ST-segment abnormalities
New Q waves
New bundle branch block
Microvoltage (<5 mm in frontal leads and <10 mm in precordial leads)
Suggests large pericardial effusion
Low voltage and a pseudoinfarction pattern in anterior
leads suggest cardiac amyloidosis.
Look for signs of electrolyte disorders and digitalis toxicity.
Chest X-ray
Dilatation of upper lobe pulmonary vessels
Kerley B lines (the only other differential diagnosis is lymphangitic carcinomatosis)
Butterfly alveolar infiltrate (may be unilateral) with prominent hila
Pleural effusions (initially on the right, then bilateral)
503
Cardiomegaly (not on an anteroposterior view!)

Suggests biventricular or left ventricular failure
Pulmonary infiltrates
Pneumonia
Normal-size cardiac silhouette does not rule out systolic or
diastolic heart failure!
Echocardiogram
Left ventricular ejection fraction and size
Normal ejection fraction is about 0.55.
Four-chamber enlargement suggests dilated cardiomyopathy.
Regional wall motion abnormalities suggest ischemia.
Diastolic dysfunction is suggested by enlarged atria and left
ventricular hypertrophy with a long deceleration time and
abnormal E/A ratio.
Valvular lesions and intracardiac structures
Pericardial diseases
Fluid
Thickening
Calcification
Blood Tests
CBC and differentialinfection, anemia
Electrolytessodium, potassium, magnesium, calcium,
phosphorous (hypophosphatemia can cause congestive heart
failure)
Serial troponins and CK-MB (every 6 hours 4)
BUN, creatinine, glucose
Always Consider the Following:

Amyloidosis (cardiac amyloidosis can occur without systemic amyloidosis)
Hemochromatosis
HIV
Myocarditis
Postpartum cardiomyopathy
Tachycardia-induced congestive heart failure
CONDITIONS THAT MIMIC CONGESTIVE HEART FAILURE

Mimic Congestive Heart Failure Clinically
COPD
504
III DISEASES
Acute respiratory distress syndrome

Pneumonia
Lung cancer
Portal hypertension
Nephrotic syndrome
Hypothyroidism
Mimic Congestive Heart Failure Radiographically

Pneumonia
Lymphangitic carcinomatosis
Noncardiac pulmonary edemaallergic, high altitude, high
intracranial pressure
Alveolar proteinosis
MANAGEMENT
Emergency Management of Heart Failure
Always consider
Does the patient need to go to the catheter lab emergently?
Does the patient need emergency echocardiography?
Does the patient need emergency cardiac surgery?
What To Do
Sit the patient upright
Administer
Oxygen
Morphine
Furosemide
Nitrates
Intra-aortic balloon pump
All Patients With Chronic Congestive Heart Failure

Sodium restriction <5 g of NaCl or 2 g of sodium daily
Physical activity based on individual exercise capacity
Daily weight assessment
Stop alcohol consumption
Angiotensin-converting enzyme (ACE) inhibitors or
angiotensin II receptor blockers (ARBs)increased survival
505
-Blockersincreased survival
Digoxinno increased survival but symptomatic improvement
Diureticsfor symptomatic relief
Hospitalized Patients Not In Cardiogenic Shock

Bed rest if in New York Heart Association functional class IV
Oxygen 2 L nasally
Heparin5,000 U SQ (or low-molecular-weight heparin)
twice daily for deep venous thrombosis prophylaxis
Intravenous diureticsevery 4-6 hours (target is weight
reduction of 0.5-1.0 kg/day)
ACE inhibitors or ARBs
Spironolactone if ejection fraction is <0.35 or patient in New
York Heart Association functional class IV
Nitrates if ischemic origin
Aspirin if ischemic
Digoxindrug of choice for patients with atrial fibrillation
Consider hemodynamically tailored therapy for refractory
or difficult-to-manage cases (see below).
Hospitalized Patients With Cardiogenic Shock or

Refractory Congestive Heart Failure
Send to catheter lab
Intensive care setting
Invasive hemodynamic monitoringtargets are the following:
Adequate right atrial pressure, >5 mm Hg
Adequate pulmonary capillary wedge pressure, >15 mm
Hg (measure of preload and filling pressures)
Systemic vascular resistance 1,000-1,200 dynes/second
per cm2 (measure of afterload)
Cardiac index >2.5 L/min per m2
Optimum mean arterial pressure (defined as minimally
acceptable blood pressure to support renal and central
nervous system function and not cause orthostatism)
Nitroprusside
For combined preload and afterload reduction desired
(high systemic vascular resistance, high pulmonary capillary wedge pressure, low cardiac index)
Use only if mean arterial pressure is 65 mm Hg, then
start at 0.1-0.2 g/kg per minute
Nitroglycerin
506
III DISEASES
For primary reduction of preload (high pulmonary capillary wedge pressure), e.g., acute pulmonary edema
Start at 0.2-0.3 g/kg per minute.
Dobutamine
For both inotropic effects and afterload reduction (high
systemic vascular resistance, low cardiac index, normal
pulmonary capillary wedge pressure)
Start at 2.5 g/kg per minute, maximal dose <20 g/kg
per minute
Dopamine
When mean arterial pressure is inadequate or as coadjuvant with dobutamine
Start at 5 g/kg per minute.
Milrinone
For combined preload and afterload reduction (high SVR,
low cardiac index, high pulmonary capillary wedge pressure)
Start at 0.5 g/kg per minute.
Intra-aortic balloon counterpulsation
If medical therapy is not sufficient
Increases mean arterial pressure, cardiac index, coronary
perfusion, and reduces afterload.
Absolute contraindications
Severe aortic insufficiency
Aortic dissection
Valuable bridge to definitive therapy but not an answer in
itself
Ventricular assist devices
May be short- or long-term bridge to cardiac transplant
Diuretics
Not usually indicated for cardiogenic shock, except in
association with acute pulmonary edema
They decrease organ perfusion and lower mean arterial
pressure.
ACE inhibitors
Not during acute shock
May be started if patient becomes stable on intra-aortic balloon pump
Heart transplant
507
III DISEASES
CONNECTIVE TISSUE DISEASES
Kenneth J. Warrington, M.D.
Steven R. Ytterberg, M.D.
SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Definition
A chronic, immune-mediated multisystem disease
The American College of Rheumatology revised classification criteria for SLE, developed primarily for research purposes, require that 4 of 11 criteria be met (Table 1).
Etiology
An unknown trigger in a genetically predisposed host results
in a sustained and injurious autoimmune response.
Epidemiology
Strong female predominance
Female:male ratio is 9:1.
Peak age at onset is 20s-30s.
Incidence rates in U.S. vary from 2.0 to 7.6/100,000 cases per
year.
Potential triggersUV light, estrogen therapy, smoking,
viral infections, drugs, environmental toxins
Clinical Presentation
General
Fever, lymphadenopathy, Raynaud phenomenon
Skin
Facial erythema is more common than classic butterfly
rash.
Malar rash, discoid lupus, photosensitivity, aphthous
ulceration
Special abbreviations used in this chapter: ANA, antinuclear antibody; BOOP,

bronchiolitis obliterans with organizing pneumonia; ENA, extractable nuclear
antigen; SLE, systemic lupus erythematosus; TNF, tumor necrosis factor.
509
Table 1. Criteria for Diagnosis of Systemic Lupus

Erythematosus
Criterion
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
Neurologic disorder
Hematologic disorder
Immunologic disorder
Antinuclear antibody (ANA)
Fixed malar erythema, flat or raised

Erythematous raised patches with keratotic
scaling & follicular plugging
Skin rash as an unusual reaction to sunlight
Oral or nasopharyngeal ulcers, usually painless
Nonerosive arthritis involving 2 or more
peripheral joints
Pleuritis or pericarditis
Persistent proteinuria (>0.5 g/day) or
Cellular casts of any type
Seizures (in absence of other causes) or
Psychosis (in absence of other causes)
Hemolytic anemia or
Leukopenia (<4 109/L on 2 or more
occasions) or
Lymphopenia (<1.5 109/L on 2 or more
occasions) or
Thrombocytopenia (<100 109/L in absence
of offending drugs)
Antidouble-stranded DNA (dsDNA) or
Anti-Smith (Sm) or
Antiphospholipid antibodies
Positive ANA in absence of drugs known to
be associated with drug-induced lupus
syndrome
Also assess for alopecia and cutaneous vasculitis.

Musculoskeletal
Arthritissymmetric, small and large joint, nonerosive
arthritis that can lead to deformity (Jaccoud arthropathy)
Myositisuncommon
Renal (glomerulonephritis)
Presents as proteinuria and/or cellular casts: red cell,
hemoglobin, granular, tubular
Renal biopsy is basis for diagnosis and classification
(Table 2).
Pulmonary
Pleurisy and pleural effusion (exudate) are common (50%70% of cases).
Definition
510
III DISEASES
Table 2. Classification of Systemic Lupus
Erythematosus According to Biopsy Findings
WHO class
Biopsy findings
I
II
III
IV
Normal
Mesangial GN
Focal proliferative GN
Diffuse proliferative GN
Membranous GN
VI
Chronic sclerosing
changes
Prognosis
Excellent
Good
Moderate
Poor, may respond to
immunosuppression
Nephrotic-range proteinuria, often with
normal creatinine
Irreversible, likely progression to renal failure
GN, glomerulonephritis; WHO, World Health Organization.
Lupus pneumonitis is rare; rule out infection first.

Otherpulmonary hemorrhage, bronchiolitis obliterans
with organizing pneumonia (BOOP), shrinking lungs
syndrome
Cardiovascular
Pericarditis and pericardial effusion (exudate) are common; tamponade is rare.
Myocardial diseasePremature atherosclerosis is a common cause of coronary artery disease, especially in young
females; coronary arteritis and myocarditis are rare.
Libman-Sacks endocarditis can cause embolic events.
Otherpulmonary hypertension, systemic hypertension
Neurologic
First, rule out infection, drug reaction, metabolic causes,
malignancy.
Headachelupus meningitis, dural sinus thrombosis,
stroke
Stroke
Infarct or hemorrhage from small-vessel vasculopathy
Embolic (Libman-Sacks endocarditis)
Antiphospholipid antibodymediated
Other causeshypertension, atherosclerosis
511
Rarevasculitis
Seizures, psychosis, cognitive function deficits
Othertransverse myelitis, optic neuritis, peripheral
neuropathy
Gastrointestinal
Abdominal pain
Secondary to medications (e.g., NSAIDs, azathioprine)
Secondary to lupusserositis (lupus peritonitis), intestinal vasculitis, pancreatitis, infarcts (liver, spleen, bowel)
Otherprotein-losing enteropathy
Hematologic
Anemiaof chronic disease (common), autoimmune
hemolytic anemia
Leukopenia, lymphopenia
Thrombocytopeniaidiopathic thrombocytopenic purpura, antiphospholipid antibodyassociated, thrombotic
thrombocytopenic purpura, drugs
Complications
Infections
Major cause of morbidity and mortality
Disease activity can be difficult to distinguish from
infection.
Always exclude infection before making diagnosis of
lupus flare.
Accelerated atherosclerosis
Secondary antiphospholipid antibody syndrome
Diagnostic Strategies
For initial SLE diagnosis
CBC, ESR, antinuclear antibody (ANA) (>99% positive,
low specificity)
dsDNA antibodies60%-80% positive, high specificity;
associated with lupus nephritis, active disease
Extractable nuclear antigens (ENAs)
Anti-Smspecific but only 7%-30% of SLE patients
are positive; associated with membranous glomerulonephritis
Anti-U1RNPlow specificity
Anti-Ro/SSA10%-50% positive, low specificity
Anti-La/SSB10%-20% positive, low specificity
512
III DISEASES
AntiScl-70uncommon, may indicate scleroderma

overlap
Complement (total, C3, C4)depressed with active
disease
Urinalysis, creatinine
aPTT, antiphospholipid antibodies, lupus anticoagulant
Assess organ involvement, depending on clinical presentation (e.g., echocardiography, MRI of head)
To assess disease activity in patient with known SLE
CBCLook for decrease in hemoglobin, WBCs, or
platelets.
ESR, dsDNA, urinalysis, creatinine, complement (total,
C3, C4)
Assess organ involvement, depending on clinical presentation.
Note: Low complement and high dsDNA may predict
disease flare.
Decrease in dsDNA can occur with active disease
because of tissue deposition.
ANA value does not vary with disease activity and does
not need to be repeated after SLE diagnosis is established.
Management
Principles of Therapy
Treatment depends on the pattern and severity of organ
involvement.
Drug therapy according to disease manifestations is listed
in Table 3.
Major Drug Complications
Hydroxychloroquineretinal toxicity
Methotrexatehepatotoxicity, cytopenias, pneumonitis
Corticosteroidsexogenous Cushing syndrome, hypertension, diabetes mellitus, osteoporosis, cataracts, avascular
necrosis of bone, adrenal suppression (give steroid prep for
major illness or surgery)
Cyclophosphamidehemorrhagic cystitis, bladder cancer,
infertility, bone marrow suppression
Mycophenolate mofetilcytopenias
513
Table 3. Drug Therapy for SLE According to Disease

Manifestations
Disease manifestation
Arthritis
Serositis
Neurologic
Hematologic
Hemolytic anemia
Thrombocytopenia
Lupus nephritis
WHO class III-IV
or mixed V/III-IV
Drug
NSAIDs
Hydroxychloroquine
Methotrexate
Prednisone
Prednisone
NSAIDs
Prednisone
Pulse cyclophosphamide IV
Typical dose
200 mg twice daily
7.5-20 mg/week
5-15 mg daily
20-40 mg daily
60 mg daily
0.5-1.0 g/m2
monthly
Prednisone
60 mg daily
Prednisone
60-100 mg daily
IV immunoglobulin 0.4 g/kg daily
5 days
Consider danazol,
cytotoxics
Pulse methylprednisolone IV
Prednisone
Pulse cyclophosphamide IV
Consider mycophenolate mofetil as
alternative
1 g/day 3 days,
then
1 mg/kg daily
0.5-1.0 g/m2
monthly
1 g twice daily
SLE, systemic lupus erythematosus; WHO, World Health Organization.
Azathioprinecytopenia, pancreatitis, hepatotoxicity, neoplasia

Note: Stopping hydroxychloroquine can result in minor and
even major disease flares.
SJGREN SYNDROME
Definition
A chronic inflammatory, autoimmune disease characterized
by progressive inflammatory infiltration of exocrine glands,
particularly lacrimal and salivary glands
Primary Sjgren syndrome occurs alone.
Secondary Sjgren syndrome occurs in association with
514
III DISEASES
other connective tissue diseases (rheumatoid arthritis, SLE,
or scleroderma).
Etiology
Unknown, but genetic factors contribute and viral infection
may be involved
Epidemiology
Strong female predominance
Age at onset is usually >40 years.
Musculoskeletalarthralgia, myalgia, myositis
Sicca manifestations
Enlargement of parotid and/or submandibular glands
Dry eyes (xerophthalmia), corneal ulceration
Dry mouth (xerostomia), difficulty chewing, dysphagia,
dental caries
Pulmonary
Cough, tracheobronchitis sicca due to dry secretions
Bronchitis, bronchiolitis
Interstitial pulmonary fibrosis
Hepaticprimary biliary cirrhosis, cryptogenic cirrhosis
Renalrenal tubular acidosis type I (due to tubulointerstitial nephritis), glomerulonephritis (uncommon)
Gastrointestinal
Dyspepsia, dysphagia
Chronic atrophic gastritis
Pancreatitis
Neurologic
Peripheral neuropathy, mononeuritis multiplex
Central nervous system (rare)focal motor deficits,
seizures, movement disorders, encephalopathy
Cutaneous vasculitis
Complications
Non-Hodgkin lymphoma
515
Relative risk in Sjgren syndrome is 44 times expected

incidence.
Patients with enlarged salivary glands and lymphadenopathy are at greatest risk.
Lab abnormalities
Anemia, leukopenia, high ESR, high C-reactive protein
Positive ANA (50%), rheumatoid factor (44%), ENA (antiRo/SSA [70%], anti-La/SSB [50%-70%])
Ocular signs
Positive Schirmer test, rose bengal staining
Lip salivary gland biopsyif positive, specificity 86.2%,
sensitivity 82.4%
Management
Symptomatic (this often is all that is necessary)
Artificial tears, lacrimal duct occlusion, artificial saliva,
pilocarpine, cevimeline
Immunomodulators
Hydroxychloroquine
Corticosteroids and cytotoxics are reserved for severe
extraglandular disease.
ANTIPHOSPHOLIPID ANTIBODY SYNDROME

Definition
This syndrome is defined as the association of the following:
Autoantibodies directed against one or more phospholipid-binding plasma proteins and/or complexes of these
proteins with phospholipids and
Venous or arterial thrombosis, recurrent fetal loss, or
thrombocytopenia
Primary antiphospholipid antibody syndrome occurs in isolation.
Secondary antiphospholipid antibody syndrome occurs in
patients with SLE or other connective tissue disease.
Epidemiology
The prevalence of primary antiphospholipid antibody syndrome is not known.
Clinically significant antiphospholipid antibody syndrome
occurs in 10% to 15% of patients with SLE.
516
III DISEASES
Thrombosis
Any part of the vascular tree can be affected
Common sites
Arterialstroke, myocardial infarction, extremity
gangrene
Venouslower limb (often with pulmonary embolus),
hepatic (Budd-Chiari syndrome), portal vein
Recurrent fetal lossusually from the late first trimester onward
Thrombocytopeniausually moderate (platelets 50109/L)
Cardiac
Noninfective verrucous vegetations (Libman-Sacks
endocarditis)
Skin
Cutaneous ulcers
Livedo reticularis
Neurologic
Migraine
Stroke
Transient ischemic attack
Transverse myelitis
Catastrophic antiphospholipid antibody syndrome
Multisystem vascular occlusion with poor prognosis (rare)
Can be precipitated by surgery, infection, stopping anticoagulation
False-positive VDRL (not done at Mayo, syphilis serology
is not helpful)
Lupus anticoagulantantibodies in patients serum that prolong certain phospholipid-dependent coagulation reactions
(e.g., aPTT and dilute Russel viper venom time are prolonged
and do not correct after equal mix with normal plasma)
Anticardiolipin antibodiesdetected with ELISA
Both lupus anticoagulant and anticardiolipin antibodies
should be checked if antiphospholipid antibody syndrome is
suspected.
517
The strongest clinical associations have been seen with IgG

anticardiolipin antibodies; however, IgM or IgA antibodies
may be associated with the syndrome.
A positive test for antiphospholipid antibody syndrome
should be confirmed by repeating in 6-8 weeks.
Diagnosis requires one of the clinical criteria (vascular thrombosis or pregnancy morbidity) and one of the lab criteria
(lupus anticoagulant or anticardiolipin antibodies).
Management
Therapy for various clinical scenarios of antiphospholipid
antibody syndrome is listed in Table 4.
DIFFUSE SCLERODERMA (SYSTEMIC SCLEROSIS)

Definition
Chronic systemic disorder characterized by microvascular
injury, inflammation, and fibrosis
Etiology
Unknown
Environmental exposures in a genetically susceptible host
may contribute.
Epidemiology
Incidence10-20 cases per million per year
Peak age at onset is 30-50 years.
Raynaud phenomenon (>95% of patients)
Usually severe
Assess for fingertip ischemia, necrosis, ulceration, pitted
scars.
Nail fold capillaroscopy is typically abnormal.
Skin
Tight, shiny, thickened skin is the hallmark feature (extending proximally above knees and elbows).
Also, telangiectasia, pigment changes, calcinosis
Pulmonary
Interstitial lung diseasedyspnea, cough, Velcro
crackles
518
III DISEASES
Table 4. Therapy for Various Clinical Scenarios of
Antiphospholipid Antibody Syndrome
Clinical scenario
Thrombosis (arterial or
venous)
Fetal loss
Prophylaxis (no event with

positive serologic test)
Catastrophic antiphospholipid antibody syndrome
Therapy
Anticoagulation with warfarin
Keep INR 3.0 (may require lifelong therapy)
5,000 U unfractionated heparin SQ
twice daily & low-dose (81 mg)
aspirin during pregnancy
Consider low-dose aspirin (81 mg
daily)
IV heparin, high-dose corticosteroids,
cyclophosphamide, plasmapheresis
(>50% mortality)
Pulmonary hypertension, usually secondary to interstitial

lung disease
Renal
Hypertension
Hypertensive renal crisis occurs in 20% of patients.
Manifests as accelerated hypertension and rapidly progressive renal failure, possibly with microangiopathic
hemolysis.
Can be precipitated by moderate to high doses of
corticosteroids
Gastrointestinal
Upper tractesophageal dysmotility, gastroesophageal
reflux, erosive esophagitis, esophageal strictures,
gastroparesis
Small bowelintestinal hypomotility, pseudo-obstruction, bacterial overgrowth, malabsorption
Colonwide-mouthed diverticula
Cardiac
Arrhythmias, myocardial fibrosis
Pericarditis (uncommon)
Musculoskeletal
519
Tendon friction rubs are typical.

Symmetric polyarthralgia, joint stiffness, finger swelling
(early)
Joint contractures (late)
Myopathy
Scleroderma is a clinical diagnosis based on typical findings.
Nonspecific findingshypergammaglobulinemia, positive
ANA (>90%), positive rheumatoid factor
Helpful serologyantiScl-70 (specific but only present in
30%)
Assess for organ involvement according to presentation,
e.g., pulmonary function tests, high-resolution chest CT,
echocardiography, gastrointestinal motility studies, renal
function variables.
Management
No known disease-modifying agent for scleroderma
Each disease manifestation requires specific management.
General
Avoid smoking.
Avoid cold exposure.
Raynaud phenomenoncalcium channel blockers (nifedipine
and amlodipine work best), angiotensin-converting enzyme
inhibitors, -blockers
Gastrointestinalproton pump inhibitor, prokinetic agents
(e.g., metoclopramide)
Musculoskeletallow-dose corticosteroids, NSAIDs,
methotrexate for synovitis
Renal
Patients with rapidly progressive skin thickening are at
greatest risk for renal crisis.
Close monitoring of blood pressure and urinalysis
Aggressive use of angiotensin-converting enzyme inhibitors
May need dialysis
Pulmonary diseasecyclophosphamide for alveolitis documented by bronchoalveolar lavage and/or high-resolution
chest CT
Pulmonary hypertensioncalcium channel blockers, bosetan
prostacyclin analogues (e.g., epoprostenol), anticoagulation
520
III DISEASES
LIMITED SCLERODERMA (CREST SYNDROME)
Definition
A variant of scleroderma
However, skin involvement does not extend proximally above
knees and elbows (although face and neck can be involved).
C, calcinosis
R, Raynaud phenomenon
E, esophageal dysmotility
S, sclerodactyly
T, telangiectasia
Not all five features need to be present for diagnosis of limited scleroderma.
Complications
Pulmonary hypertension (usually in the absence of pulmonary parenchymal disease)
Renal disease is rare in this subset of patients.
Limited scleroderma is a clinical diagnosis based on typical
findings.
Helpful serologic test is anti-centromere antibody (specific,
present in 50%).
Assess for organ involvement according to presentation, e.g.,
pulmonary function tests, echocardiography for pulmonary
artery pressure, and gastrointestinal evaluation.
Management
Disease manifestations are treated individually (see DIFFUSE
SCLERODERMA, Management).
RHEUMATOID ARTHRITIS
Definition
Chronic, autoimmune, inflammatory disorder characterized
by erosive, symmetric arthritis with a variable degree of
extra-articular involvement
521
Presence of four of the seven following criteria have 90%

sensitivity and specificity:
Morning stiffness >1 hour 6 weeks
Arthritis >3 joints simultaneously 6 weeks
Hand joint arthritis 6 weeks
Symmetric joint involvement 6 weeks
Rheumatoid nodules
Positive rheumatoid factor
Radiologic findings
Etiology
Unknown
Genetic factors (HLA genes in particular) are important.
Epidemiology
Prevalence rate is about 1%.
Female:male ratio is 2-3:1.
Age at onset is 40-60 years.
Systemicfatigue, myalgias
Musculoskeletal
Symmetric, erosive, small and large joint polyarthritis,
which is often progressively deforming
Assess for ulnar deviation, swan neck, boutonnire
deformity.
Tenosynovitis, bursitis
Extra-articular disease
Skin
Subcutaneous nodules (20%-30% of rheumatoid factorpositive patients)
Nail-fold infarcts
Eyessecondary Sjgren syndrome, scleritis, scleromalacia
Pulmonarypleurisy, pleural effusion, rheumatoid lung
nodules, BOOP, fibrosis
Cardiacpericarditis, myocarditis, rheumatoid nodules
(valve, myocardium)
Felty syndromesplenomegaly, large granular lymphocytosis, neutropenia
Neurologicentrapment neuropathy (e.g., carpal tunnel),
mononeuritis multiplex
522
III DISEASES
Complications
InfectionRheumatoid arthritis and its treatment predispose to infection.
If infection is suspected or documented, consider withholding immunosuppressive agents.
Always rule out septic arthritis if one joint is inflamed
out of proportion to other joints.
Carefully assess any prosthetic joints if infection is suspected.
Tumor necrosis factor (TNF) blockade can predispose to
TB reactivation, opportunistic lung infection.
Atlantoaxial subluxation
Spinal cord compromise
Obtain lateral flexion and extension cervical spinal films.
Careful neurologic assessment for evidence of radiculopathy or myelopathy
Vasculitis
Polyarteritis nodosa-like illness, usually in patients with
chronic, severe, deforming, nodular rheumatoid arthritis
Can present as mononeuritis multiplex, leg ulcers, mesenteric ischemia
Treat with high-dose corticosteroids and cytotoxic agents.
Premature mortalitymainly cardiovascular and infectious
causes
Amyloidosis
Rheumatoid arthritis is a major cause of secondary
amyloidosis.
Adrenal suppression
If patient is receiving long-term corticosteroid therapy,
steroid prep may be needed during major illness/surgery
(50-100 mg hydrocortisone every 8 hours for 1-2 days or
until stable, then resume usual dose).
Osteoporosis
Rheumatoid arthritis is a clinical diagnosis, based on history
and physical exam.
Nonspecific lab abnormalitiesanemia, high ESR, high Creactive protein, thrombocytosis
523
Positive rheumatoid factor75%-80% of patients with

rheumatoid arthritis are positive, but test is not specific
Radiologyhand and foot X-rays to look for erosive changes
Management
Needs to be individualized depending on patient characteristics, disease course, drug tolerability, drug toxicity, concurrent illness
Disease-modifying antirheumatic drugs commonly used to
treat rheumatoid arthritis and their major toxic effects are
listed in Table 5.
SERONEGATIVE SPONDYLOARTHROPATHIES
Definition
Group of disorders that includes the following:
Enteropathic arthritis (inflammatory bowel diseaseassociated arthropathy)
Reiter syndrome (reactive arthritis)
Psoriatic arthritis
Common features of seronegative spondyloarthropathies
Absence of rheumatoid factor
Association with HLA-B27
Axial skeletal involvement with sacroiliitis and spondylitis
Asymmetric oligoarthritis of large weight-bearing joints
Dactylitis (inflammation of a digit)
Enthesitis (inflammation of bony insertions for tendons and
ligaments)
Specific Disease Features
Ankylosing Spondylitis
Needs to include the skeletal manifestations and radiographic
findings
Cause not known (exclude other causes of spondyloarthropathy listed above)
Male:female ratio is 3:1; age at onset is adolescence to 35
years.
Extraskeletal manifestations
Aortic valve regurgitation (~5% of patients), complete
heart block
Apical lung fibrosis (1% of patients)
524
III DISEASES
Table 5. Disease-Modifying Antirheumatic Drugs
(DMARDs) Used to Treat Rheumatoid Arthritis
DMARD
Hydroxychloroquine
Methotrexate
Sulfasalazine
Azathioprine
Gold (injectable)
Cyclosporine
Leflunomide
Infliximab
Etanercept
Adalimumab
Anakinra
Typical dose
400 mg/day
Toxic effect
Retinal damage
7.5-25 mg weekly
Hepatotoxicity, acute
interstitial pneumonia,
cytopenias
500-2,000 mg/day Leukopenia
2-2.5 mg/kg daily
Leukopenia, hepatotoxicity, lymphoma
25-50 mg/week IM Leukopenia, thrombocytopenia, pneumonitis,
glomerulonephritis
3-4 mg/kg daily
Renal dysfunction,
hypertension
100 mg/day 3
Hepatotoxicity
days, 20 mg/day
3 mg/kg at 0, 2, 6
Infusion reactions, TB
weeks, then IV
reactivation, opportunisinfusion every 8
tic lung infections
weeks
25 mg SQ twice
Injection site reactions,
weekly
infection, demyelinating
disease
40 mg SQ every
other week
infection, demyelinating
disease
100 mg/day SQ
neutropenia
Thoracic cage restriction from costovertebral fusion

Uveitis (25% of patients)
Renal amyloidosis
Complications
Vertebral fractureseven after minimal trauma (because
of spine rigidity and osteopenia)
Cauda equina syndromepresents as sensory loss in lum
525
bar and sacral dermatomes, lower limb weakness and pain,

and loss of urinary and rectal sphincter tone
Management
Physical therapy
NSAIDs
Sulfasalazine
TNF blockade
Enteropathic Arthritis
Associated with inflammatory bowel disease (Crohn disease and ulcerative colitis)
Sex ratio is equal; age at onset is 25-44 years.
Arthritis occurs in 2%-20% of patients with inflammatory
bowel disease.
Peripheral arthritis often correlates with activity of gut
inflammation; axial disease does not.
Axial disease is clinically and radiographically identical to
idiopathic ankylosing spondylitis.
Management
Treat gastrointestinal disease.
Consider sulfasalazine, methotrexate, TNF blockade.
Reiter Syndrome (Reactive Arthritis)

Acute inflammatory arthropathy arising after an infectious
process, but at a site remote from the primary infection
Common pathogens associated with the syndrome include
Shigella, Salmonella, Yersinia, Campylobacter (enteric infections), Chlamydia, Ureaplasma, and HIV (genitourinary
infection).
Classic triad of urethritis, conjunctivitis, and arthritis occurs
in 33% of patients.
Other extraskeletal manifestations include circinate balanitis, keratoderma blennorrhagicum, and mucosal ulcers.
Management
Physical therapy
NSAIDs
Immunosuppression for chronic disease
Majority of patients have self-limiting disease.
Psoriatic Arthritis
Occurs in 5%-7% of patients with psoriasis; sex ratio is equal.
526
III DISEASES
May manifest as
Spondyloarthropathy
Symmetric polyarthritis resembling rheumatoid arthritis
Distal interphalangeal joint arthritis
Arthritis mutilans (associated with osteolysis of affected
joints)
Oligoarticular arthritis
Assess for characteristic nail changes, including pitting, onycholysis, and subungual hyperkeratosis.
Management
NSAIDs
Methotrexate
TNF blockade
Other agents used for rheumatoid arthritis
527
III DISEASES
DIABETES MELLITUS
Gunjan Y. Gandhi, M.D.
Pierre Theuma, M.D.
Victor M. Montori, M.D.
DEFINITION
Fasting plasma glucose >126 mg/dL (7 mmol/L) and confirmed at least once on repeat measurement (normal if <100
mg/dL)
Random glucose >200 mg/dL plus symptoms of diabetes
mellitus
CLASSIFICATION
Type 1
Type 2
Secondary diabetesdrugs, endocrinopathies, exocrine pancreatic disease, infections, genetic syndromes
Gestational diabetes
ETIOLOGY
Type 1results from immune-mediated destruction of
insulin-producing -cells of endocrine pancreas, could be
idiopathic
Type 2results from insulin resistance and some degree of
defective insulin production related to visceral obesity and
sedentary lifestyle
EPIDEMIOLOGY
Diabetes affects 6% of U.S. population, and 18% of population older than 60
Diabetes is more common among American Indians,
Alaska Natives, and African Americans; prevalence is
similar for Hispanics and non-Hispanic whites
No difference between sexes
529
Common clinical presentations of type 1 and type 2 diabetes
are compared in Table 1.
MANAGEMENT
Routine Management of Diabetic Patients on Hospital
Service
In acutely ill patients or during immediate perioperative
period, normoglycemia is the currently recommended ideal.
Perioperative
Goals of hospital care
Maintain normoglycemia
Prevent hypoglycemic episodes and ketoacidosis.
Patients on oral agents or diet control may need insulin
therapy during the acute stress of major surgery and critical illness.
IV insulin infusions are preferred to SQ route during the
immediate postoperative period (e.g., after cardiac and
vascular surgery). This ensures adequate insulin delivery in case of peripheral shutdown in the perioperative
period and also makes it possible to carefully titrate insulin
to frequently measured blood glucose levels.
Tight glycemic control with insulin improves outcomes of
patients in ICU.
Currently, there is no consensus on intraoperative management of hyperglycemia.
Note: Measure glucose every half hour during the operation
and in postanesthesia recovery room. An insulin infusion
may be used intraoperatively. Goal has not been established.
Table 1. Comparison of Common Clinical Presentations

of Type 1 and Type 2 Diabetes
Type 1
Fatigue
Weight loss
Polyuria
Polyphagia
Polydipsia
Severe dehydration
530
Type 2
Asymptomatic or incidental finding
End-organ damage
Recurrent infections
Visual blurring
III DISEASES
Measure immediate postoperative glucose level.
If >80 mg/dL, see Table 2 for insulin infusion algorithm (your hospital may have implemented a different algorithm), especially in cardiac surgery patients.
On day of surgery, omit sulfonylurea
Stop metformin before any contrast study
Current guidelines recommend that patients not restart
metformin any sooner than 48 hours after contrast study
or surgery and only if renal function is stable and normal,
i.e., creatinine <1.5 mg/dL in men, <1.4 mg/dL in women
(potential risk of lactic acidosis)
The common practice of sliding scale administration of regular insulin doses every 6 hours based on reflectance meter
glucose results does not provide proper control.
Insulin-treated patients could receive the usual insulin
dose on the day before the operation.
On the day of the operation, give half the usual morning
dose of NPH or Lente insulin SQ.
If the patient is on Ultra-Lente insulin, the entire dose
may be given the evening before the operation.
The algorithm in Table 2 should not be used for patients with
diabetic ketoacidosis or hyperosmolar states.
A typical insulin infusion is 250 U Human Regular insulin
in 250 mL of 0.45% sodium chloride.
DIABETIC EMERGENCIES
Check blood glucose levels in patients with glycosuria, in
any ill diabetic patient, and in any patient with a clinical
state in which derangement of blood glucose must be excluded (Table 3).
Hypoglycemia
Diagnosis
Whipple triad
Suggestive symptoms
Low plasma glucose level (<50 mg/dL in men, <40 mg/dL
in women)
Prompt symptomatic relief with glucose administration
531
532
Table 2. Insulin Infusion Protocol

Column 1
Start in this column
Restart in this column when insulin
infusion had to be discontinued for
glucose <80 mg/dL
Column 2
Patient has not reached glucose range of
80-100 mg/dL within 2 hours using
column 1 and glucose has decreased by
<50 mg/dL over preceding 1 hour
Column 3
Patient has not reached glucose range
of 80-100 mg/dL within 2 hours using
column 2 and glucose has decreased by
<50 mg/dL over preceding 1hour
Serum glucose,
mg/dL
Serum glucose,
mg/dL
Insulin infusion
rate, units/hour
Serum glucose
mg/dL
Insulin infusion
rate, units/hour
>400
351-400
301-350
251-300
201-250
176-200
151-175
121-150
101-120
80-100
<80
18
16
14
12
10
8
6
4
2
1
Off
>400
351-400
301-350
251-300
201-250
176-200
151-175
121-150
101-120
80-100
<80
25
22
20
18
15
12
9
7
4
2
Off
>400
351-400
301-350
251-300
201-250
176-200
151-175
121-150
101-120
80-100
<80
When glucose is <80 mg/dL, stop insulin infusion and initiate 50 mL/h of 10% dextrose in water.
Check glucose every 30 minutes until glucose is 80 mg/dL. Discontinue D10W. Resume insulin infusion, always in column 1.
If glucose is <60 mg/dL, initiate Treatment of Hypoglycemia Protocol (MC1156-30).
Restart insulin infusion in column 1 when glucose 80 mg/dL.
Check arterial blood glucose every 1 hour in the ICU once insulin infusion has been started.
Insulin infusion
rate, units/hour
30
27
24
21
18
15
12
9
6
3
Off
III DISEASES
Etiology
Causes of hypoglycemia are listed in Table 4.
Management
If the patient is not able to take oral feeding safely, then NPO
Administer 25 mL of 50% dextrose in water IV over 3-5
minutes in a large vein immediately and repeat every 1520 minutes if needed.
If this is not feasible, give glucagon 1 mg SQ (preferred)
or IM.
Table 3. Clinical States in Which Glucose Derangements

Should Be Excluded
Acute confusion
Seizures
Suspected stroke
Decreased level of consciousness
Sepsis
Hypothermia
Liver failure
Metabolic acidosis
Salicylate poisoning
Severe hyponatremia
High-dose corticosteroid use
Table 4. Causes of Hypoglycemia

Common mismatch between hypoglycemic agent and caloric intake
Insulin excess (decreased renal function, erratic absorption)
Oral hypoglycemic agent excess
Severe liver disease
Severe sepsis
Alcohol excess, especially after a binge
Less common causes
Adrenal failure
Salicylate poisoning
Insulinoma
Hypopituitarism
533
Recheck blood glucose level by capillary stick test after 15

minutes of initial treatment.
Repeat treatment if blood glucose is <80 mg/dL and monitor. Repeat until blood glucose is >80 mg/dL.
If patient is alert and can swallow, give 15 g of carbohydrates:
Half cup of fruit juice, 2 packets of sugar dissolved in half
cup of water, or glucose oral gel 15 g PO
Then provide a snack to prevent recurrence
Consider and treat the underlying cause (Table 4).
Exclude artifactual hypoglycemia or possibility of lab error.
Do not rely only on blood glucose measurements by glucose-monitoring devices.
If hypoglycemia recurs or is likely to recur (sepsis, excessive
sulfonylurea therapy, or long-acting insulin)
Start 5% or 10% dextrose infusion at 75 mL/hour in a
large peripheral or central vein.
Check the reflectance meter glucose regularly, and adjust
the infusion rate to keep the blood glucose level in normal
range.
In sulfonylurea excess (especially long-acting preparations such as glyburide or chlorpropamide), maintain
glucose infusion for 24 hours, then taper off over the
next 2-3 days.
If alcohol excess is suspected, add thiamine IV to the infusion to prevent Wernicke encephalopathy.
If the response to 10% glucose is not sufficient, give more
50% dextrose, preferably in a central vein.
Consider the diagnosis in any ill patient who has diabetes.
Exclude this diagnosis for patients with confusion, coma,
or metabolic acidosis who have increased anion gap.
Pathophysiology
Severe insulin deficiency with or without excess counterregulatory hormones (glucagon, epinephrine)
Diagnosis
Hyperglycemia >250 mg/dL (13.9 mmol/L)
Ketonemia/ketonuria (check -hydroxybutyrate if available)
Metabolic acidosis with increased anion gap
534
III DISEASES
Etiology
In diabetic patients
Insulin deficiency (missed doses, failure to increase dose
with illness)
Infection
Inflammation
Myocardial ischemia, infarction
Glucocorticoid administration
Presenting feature in patients with previously undiagnosed
type 1 diabetes
Often characterized by a gradual deterioration, sometimes
over days
Anorexia, nausea, vomiting, polyuria, and subsequent
dehydration
Abdominal pain may be present.
Kussmaul respiration (deep and rapid), acetone breath
If untreated, altered consciousness or frank coma
Order priority
Blood glucose level (reflectance meter glucose and lab)
Ketones (plasma and urine)
Electrolyte panel
Blood cultures
ECG
Chest X-ray
Urinalysis and Gram stain
Evaluate anion gap (sodium, chloride, bicarbonate)
Management
Consider transfer to medical ICU.
Fluids
Deficit is usually 5-8 L, and both free water and salt are
required.
Aggressive hydration needs to be initiated (may require
535
boluses, depending on clinical assessment of hydration

state)
Rate initially, 10-14 mL/kg per hour of 0.9 normal saline
May need to titrate based on cardiovascular status
Insulin
Immediately give 10-20 U (0.15 U/kg body weight) regular insulin as IV bolus.
Start insulin infusion at 0.1 U/kg body weight per hour, and
titrate to blood glucose level of 200-250 mg/dL.
Adjust infusion rate to decrease glucose by 50 mg/dL per
hour.
Aim to reverse ketosis in the first 24 hours, avoid hypoglycemia, and avoid cerebral edema from too rapid a
decrease in osmolality.
Stop insulin infusion when the anion gap has resolved.
Overlap the infusion with SQ insulin by 2-3 hours.
Monitor reflectance meter glucose every 4 hours.
When glucose is 250 mg/dL, change to 5% dextrose plus
0.45 NaCl with insulin coverage (e.g., 200 mL/hour infusion with 0.05 U/kg per hour IV or 5-10 U SQ every 2
hours). Goal is 150-200 mg/dL glucose until metabolic
control is achieved.
Monitor electrolytes.
Potassium deficit is about 300-500 mEq independently
of serum potassium; the total body stores are low and will
decrease further with therapy. If renal perfusion and urinary flow are adequate, add 40 mEq of potassium to each
liter of IV fluid.
Replace phosphate if <1 mg/dL. Give 20-30 mEq/L of
potassium phosphate IV over 6 hours.
Bicarbonate may be given if pH is <7.1 and systolic blood
pressure is <90 mm Hg despite fluid replacement. Avoid
excess bicarbonate because it will exacerbate hypokalemia
and lead to paradoxical CSF acidosis.
Hyponatremia may be present because of osmotic water
shifts or as pseudohyponatremia due to hyperglycemia
(for every increase in glucose of 100 mg/dL over 100
mg/dL, sodium decreases by 1.6 mmol).
Treat underlying cause
Check for a focus of infection, including the feet and
perineum.
536
III DISEASES
Fever may be absent despite infections.
Consider empiric antibiotic therapy, including anaerobic
cover.
Leukocytosis does not necessarily imply infection but
may be due to diabetic ketoacidosis itself.
Monitor pH, bicarbonate, anion gap, ketones (including hydroxybutyrate), glucose, potassium, and urine output every
1-2 hours, keeping track of vital signs, IV fluid rate and composition, and insulin infusion.
HYPEROSMOLAR NONKETOTIC HYPERGLYCEMIC COMA

Consider the diagnosis for any patient with hyperglycemia,
hyperosmolality, change in mental status, and no ketoacidosis.
Etiology
Same as for diabetic ketoacidosis; in addition, dehydration
and renal failure
Mostly affects elderly patients who have type 2 diabetes.
Circulating insulin prevents ketogenesis.
Features
Mental obtundation, polyuria, nausea, vomiting
Extreme dehydration, orthostatic hypotension, tachycardia
Reversible hemiplegia, focal seizures
Diagnosis
Order priorityserum osmolality, blood cultures, LDH,
CBC, electrolyte panel (including magnesium), phosphate,
urine culture and stain, urinalysis, arterial blood gases, ECG,
chest X-ray
Often, the blood glucose level is >600 mg/dL (>33.3
mmol/L), serum osmolality >340 mOsm/L, BUN 60-90
mg/dL. Lactic acidosis may be present.
Sodium is decreased (normal or increased, if severe dehydration)correct by 2.4 mEq/L per 100 mg/dL glucose over
100 mg/dL.
537
Bicarbonate is usually >12 mEq/L (average, 17), pH >7.2

(average, 7.26).
Decreased calcium, magnesium, potassium, and inorganic
phosphorus
Management
Consider transfer to medical critical care unit.
Coma rarely occurs unless the calculated effective osmolality is >320 mOsm/L
Serum osmolality = 2 (sodium + potassium) + (plasma glucose/18) + (BUN/2.8)
Fluids
Mean fluid loss is 9L, thus, aggressive hydration (1 L normal saline per hour)
Start normal saline infusion if hypotensive
Change to 5% dextrose plus 0.45 normal saline after blood
glucose level reaches 300 mg/dL
Maintain blood glucose at 250-300 mg/dL until osmolality is 315 mOsm/kg and patient is alert.
Insulin
Use same insulin algorithm for diabetic ketoacidosis.
Potassium
Correct hypokalemia (serum potassium level <3.3 mEq/L)
Withhold insulin.
Administer 40 mEq potassium (2/3 potassium chloride,
1/3 potassium phosphate)
If potassium level is
3.3-5.5 mEq/L, give 20 mEq/L potassium IV
>5.5 mEq/L, recheck every 2 hours.
538
III DISEASES
EPILEPTIC SEIZURES
Yoon-Hee K. Cha
Gregory A. Worrell, M.D.
Gregory D. Cascino, M.D.
DEFINITIONS
Seizuretransient episode of disturbed cerebral function
caused by abnormal excessive synchronous electrical discharge of cortical neurons
Provoked seizuresa symptomatic seizure caused by a precipitating factor (e.g., fever, drugs, ethanol withdrawl, electrolyte abnormalities)
Epilepsychronic medical condition characterized by recurrent unprovoked seizures
Status epilepticuslife-threatening condition defined by
continuous seizures for 5 minutes or 2 seizures with
incomplete recovery of consciousness between seizures
(older definition of status epilepticus: seizures lasting >30
minutes)
CLASSIFICATION OF EPILEPSY
The International Classification of Epileptic Seizures is given
in Table 1, and the features distinguishing secondarily generalized from primarily generalized seizures are listed in Table 2.
EPIDEMIOLOGY OF SEIZURES, EPILEPSY, AND
STATUS EPILEPTICUS
Seizures
10% lifetime risk
Account for 1% of emergency department visits
Epilepsy
3%-4% lifetime risk, with 0.5%-1% prevalence
Status epilepticus
Special abbreviations used in this chapter: AED, antiepileptic drug; CNS, central
nervous system.
539
Table 1. International Classification of Epileptic Seizures

Partial seizures (focal onset)
Simple partial seizures (normal consciousness)
Motor signs
Somatosensory or special-sensory symptoms (olfactory,
visual, taste)
Autonomic symptoms or signs (e.g., epigastric rising
sensation)
Psychic symptoms (e.g., dj vu, jamais vu, fear)
Complex partial seizures (impaired consciousness)
No impairment of consciousness at onset
Without automatisms
With automatisms (picking at clothes, lip smacking,
complex motor behaviors)
With impairment of consciousness at onset
Without automatisms
With automatisms
Partial seizures secondarily generalized (see Table 2)
Generalized seizures (bihemispheric at onset)
Absence or atypical absence seizures (may have mild clonic,
atonic, tonic, or autonomic activity or automatic behavior)
Myoclonic seizures
Clonic seizures
Tonic seizures
Tonic-clonic seizures
Atonic seizures
Unclassified epileptic seizures
Modified from Mosewich RK, So EL. A clinical approach to the classification of seizures and epileptic syndromes. Mayo Clin Proc. 1996;71:405-14.
By permission of Mayo Foundation for Medical Education and Research.
50/100,000 persons, with 22% mortality

Incidence is highest for patients <1 year old, patients >60
years make up largest group.
Mortality from status epilepticus
Pediatric, 2.5%
Adults, 14%
Adults >60 years, 38%
CAUSE OF SEIZURES
Vascularsubarachnoid hemorrhage, venous sinus thrombosis, ischemic stroke, intracranial hemorrhage, hypertensive
encephalopathy, arteriovenous malformation
540
III DISEASES
Table 2. Evidence for Secondarily Generalized Versus
Primarily Generalized Seizure
Preceeding aura (e.g., epigastric rising sensation, tastes, smells, psychic)
Preceeding motionless period with unresponsiveness and staring
Preceeding automatisms (e.g., lip smacking, chewing, picking,
complex patterned movements)
Preceeding focal or asymmetric motor phenomena (e.g., tonic or
dystonic posturing, clonic jerking, head or eye deviation)
Any of the above occurring occasionally in isolation without generalization or loss of consciousness
Focal abnormalities on neurologic exam
Focal epileptiform activity on EEG
Focal abnormality on MRI (e.g., hippocampal atrophy, tumor,
infarct, vascular malformation, hamartoma, cortical dysplasia,
encephalomalacia)
Modified from Mosewich RK, So EL. A clinical approach to the classification of seizures and epileptic syndromes. Mayo Clin Proc. 1996;71:405-14.
By permission of Mayo Foundation for Medical Education and Research.
Infectionmeningitis, encephalitis (e.g., California virus,

herpes simplex), abscess
Toxicdrugs/drug withdrawal, ethanol, carbon monoxide,
lead, strychnine, mercury (review patients medicines for
ability to provoke seizures)
Autoimmune/inflammatorythrombotic thrombocytopenic
purpura, central nervous system (CNS) vasculitis, multiple
sclerosis
Metabolichypoglycemia, nonketotic hyperglycemia,
hyponatremia, hypocalcemia, hypomagnesemia, hypoxia,
pyridoxine deficiency
Traumapenetrating head trauma, subdural or epidural
hematoma
Neoplasmprimary CNS tumor (e.g., astrocytoma, meningioma, oligodendroglioma, lymphoma), metastatic lesion
(e.g., lung, breast, melanoma, lymphoma)
Genetic and congenitalprimary idiopathic epilepsy, tuberous sclerosis, Sturge-Weber syndrome, neurofibromatosis,
perinatal injury (infection, hypoxia, birth trauma)
541
Epilepsypatient with known epilepsy and a subtherapeutic antiepileptic drug level, infection, or other underlying
medical condition
Common causes of symptomatic seizures by age are listed in
Table 3.
Clinical presentationcan range from obvious (e.g., generalized tonic-clonic seizure) to subtle changes in awareness, behavioral, emotional, or psychic symptoms
Alteration of consciousnessassociated with both generalized seizures (e.g., absence and tonic-clonic) and complex
partial seizures
Nonconvulsive status epilepticusvaried presentations ranging from alterations of consciousness to coma
DIAGNOSTIC STRATEGY
Simultaneous EEG and clinical observation of the seizure
provide the definitive diagnosis of seizure type. The most
common situation is a patient who has had a seizure without
a physician observing the clinical event. For this reason,
the most important diagnostic tool is the history.
The history should be taken from an eyewitness observer if
possible. When necessary, telephone persons who have witnessed the patients clinical events.
Table 3. Common Causes of Symptomatic Seizures by Age

Age, years
5-15
15-35
35-64
65
542
Cause
CNS infection
Head trauma
Ethanol withdrawal
Head trauma
Eclampsia
Ethanol withdrawal
CNS tumor
Trauma
Stroke
Stroke
Metabolic
III DISEASES
History
Ask about the common risk factors for epilepsy, including:
Family history (genetic predisposition to seizure disorder)
Birth history and complications, cognitive and motor
development
Infant or childhood seizures (e.g., febrile seizures are associated with temporal lobe epilepsy)
Past history of CNS infections, stroke, head trauma, cancer (see causes listed above)
Detailed description of the eventSeizures are generally
brief and have stereotyped patterns.
What was patient doing at time of the event, e.g., did the
seizure occur during sleep?
Were there any warning symptoms/aura and were they
focal (Table 2)?
Did the patient lose consciousness?
What other symptoms were present (e.g., shortness of
breath or chest pain may suggest a different diagnosis)?
How long did the event last (most seizures last <3
minutes)?
Description of the movementsDid patient fall to the
ground?
Did patient lose bowel/bladder control or bite the tongue?
Was there postictal confusion?
The history can suggest other possible diagnoses for transient neurologic symptoms and loss of consciousness,
including:
Syncope (presyncopal symptoms, precipitating maneuvers, orthostatic blood pressure, abnormal ECG)
Sleep disorders such as narcolepsy
Stroke (posterior circulation)
Migraine
Paroxysmal vertigo
Transient global amnesia
Ethanol/drug-related blackouts
Movement disorder (myoclonus, dyskinesias)
Psychiatric (nonepileptic seizures, panic attacks, hyperventilation)
543
Physical Exam
Vital signs, including oxygenation status
Detailed exam with attention to the following:
Level of consciousnessIn unresponsive patients, subtle rhythmic movements of limbs or eyes may indicate
ongoing seizure activity.
Headsigns of trauma
Cranial bruitsvascular malformation
Cervical bruitcarotid stenosis
Focal neurologic deficits may indicate a structural lesion
hemiparesis, asymmetric reflexes, sensory deficit, visual
field defect, memory deficit
Cardiac arrhythmia and/or murmurs
Skinstigmata of neurocutaneous syndromes
Lab Testing
Baseline CBC, sodium, potassium, calcium, magnesium,
BUN, creatinine, glucose, liver function tests, PT, PTT,
arterial blood gases, VDRL, toxin screen, antiepileptic drug
(AED) levels, chest X-ray, and ECG
Same night
Head CT (without contrast)to rule out structural lesions,
head trauma, or bleeding
Lumbar puncture if infection is suspected (perform CT
first if neurologic exam is abnormal, patient is >60 years
old or is immunocompromised)
EEG if ongoing subclinical seizure activity is suspected
(consider nonconvulsive status epilepticus for patients
with persistent mental status alterations)
Outpatient evaluation
MRIthe imaging modality of choice for evaluation of
seizure disorders
EEGsleep and awake EEG (diagnostic yield is increased
with sleep deprived recording)
COMPLICATIONS
The most common complication associated with seizures is
physical trauma suffered during the event (e.g., falling, automobile accident, drowning).
Hypoxia, hyperthermia, hypotension, and hypoglycemia can
complicate prolonged seizures and status epilepticus.
544
III DISEASES
Generally, the longer that status epilepticus continues, the

more difficult it is to control.
MANAGEMENT (ADULTS)
General indications for AEDs are listed in Table 4.
Acute Management
Seizures are usually self-limited (<3 minutes) and rarely
require emergency intervention.
Overly aggressive therapy with benzodiazepines and other
AEDs can have dangerous consequences (e.g., hypotension,
respiratory depression, cardiac arrhythmia).
Table 4. General Indications for Antiepileptic Drugs

(AEDs)
AED
Seizure type
First line
Second line
Third line
Partialsimple,
Carbamazepine Lamotrigine
Felbamate
complex, with/
Phenytoin
Levetiracetam Phenobarbital
without secondary
Topiramate
generalization
Gabapentin
Generalized
Classic absence Ethosuximide Valproic acid Felbamate
Lamotrigine
Atypical absence Valproic acid Topiramate
Felbamate
Lamotrigine
Tonic-clonic
Valproic acid Carbamazepine Felbamate
Phenytoin
Clonazepam
Lamotrigine
Topiramate
Myoclonic
Valproic acid
Felbamate
Lamotrigine
Clonazepam
Phenobarbital
Tonic, atonic,
Valproic acid Lamotrigine
Phenytoin
akinetic, clonic,
Felbamate
or mixed
Clonazepam
Infantile spasms
ACTH
Prednisone
Clonazepam
ACTH, adrenocorticotropic hormone.
545
Procedure
Position patient on his/her side and in location where no
harm is likely during a convulsion (e.g., falling out of bed,
injury from sharp furniture).
Maintain an airway and ensure adequate oxygenation (face
mask oxygen if needed).
Monitor vital signs (oxygen saturation, blood pressure,
pulse, respiratory rate, temperature).
Check finger stick glucose.
Draw blood sample for routine lab tests and AED levels;
establish IV line if needed.
Record accurate time of duration of seizure.
If a generalized tonic-clonic or tonic seizure lasts >3
minutes, begin treatment with IV lorazepam (2 mg initial dose) and consider loading with fosphenytoin (20
mg/kg) (Fig. 1).
If the seizure continues, follow algorithm in Figure 2.
Seizure precautions should be implemented, including
padding the bed rails; restraints should not be used.
Long-Term Management
General guidelines for starting long-term AED therapy are
given in Table 5.
Not all patients require an AED after a seizure.
If the evaluation is normal and no risk factors are identified,
the risk of a second seizure is approximately 25%.
The risk of recurrence after a second seizure is 65%-80%.
Discuss the following with all patients:
Risk of injury if they have a seizure while driving, operating dangerous equipment, or swimming; driving laws
vary by state (see Epilepsy Foundation Web site
http://efa.org)
Women with epilepsy
AED therapy is associated with teratogenesis.
All women require folic acid supplementation of 0.4
mg/day.
Attempt to plan pregnancy with help of physicians (neurologist and obstetrician)
Some AEDs decrease the effectiveness of oral contraceptives.
546
Lorazepam (Ativan):
give 2 mg every 1 minute **
Seizures continue
Phenytoin 20 mg/kg IV at 50 mg/minute or fosphenytoin at

20 mg/kg PE at 150 mg/minute
Seizures continue
Fig. 1. Acute management for seizures
Minutes
25
Phenytoin or fosphenytoin (additional 5-10 mg/kg or 5-10 mg/kg PE

Seizures continue
40
Phenobarbital 20 mg/kg at 50-75 mg/minute
Proceed directly to anesthesia if patient develops status in ICU, has severe

systemic disturbance, or seizures have continued >60-90 minutes
60
Phenobarbital (additional 5-10 mg/kg)

Seizures continue
>60
547
Proceed to anesthesia with propofol

or midazolam (Versed)
III DISEASES
Seizures continue
lasting more than 3 minutes. PE, phenytoin equivalents. More lorazepam can
be given. **If emergent IV access cannot
be obtained, use rectal diazepam 0.5
mg/kg. (Modified from Lowenstein DH,
Alldredge BK. Currect concepts. Status
epilepticus. N Engl J Med. 1998;338:9706. Used with permission.)
Assess & control airway

Monitor vital signs (including temperature)
Conduct pulse oximetry & monitor cardiac
function
Perform rapid blood glucose assay
Start IV infusion
Administer thiamine (100 mg) & glucose
(50 mL of 50% dextrose)
Start anticonvulsant therapy

per Figure 1
Take focused history & examine patient
Known seizure disorder or other illnesses?

Trauma?
Focal neurologic signs?
Signs of medical illnesses (e.g., infection,
hepatic or renal disease, substance abuse)?
Perform lab studies
CBC
Serum electrolytes & calcium
Arterial blood gas
Renal function
Toxicology
Serum AED concentrations
Undertake further work-up to

define cause
Manage other medical problems
Fig. 2. Emergency management of status epilepticus. AED, antiepileptic

drug. (From Lowenstein DH, Alldredge BK. Current concepts. Status
epilepticus. N Engl J Med. 1998;338:970-6. Used with permission.)
548
III DISEASES
Table 5. Guidelines for Starting Long-term Therapy With
Antiepileptic Drugs
Treat
Maybe treat
Status epilepticus as Uncomplicated single

a first seizure
seizure if history sugMRI/CT lesion
gests that one occurClear-cut epileptic
red earlier
focus on EEG
Single seizure in someActive or previous
one at risk if seizure
CNS infection
recurs (drivers, home
Abnormal neurologic alone, etc.)
exam findings
Head injury with
loss of consciousness
History of epilepsy
in siblings/parents
Do not treat
Ethanol withdrawal
or other provoked
seizure
Substance abuse (if
due to barbiturate
abuse, should replace the drug &
taper slowly)
Sleep deprivation
Febrile seizures
Seizures due to
acute illness that is
resolving
Nonepileptic spells
Epilepsy with
centrotemporal
spikes
549
III DISEASES
FULMINANT HEPATIC FAILURE
Thomas C. Sodeman, M.D.
J. Eilene Hay, M.B., Ch.B.
DEFINITION
Hepatic dysfunctionjaundice, increased PT, low albumin
Encephalopathy
No previous history of liver disease
CLASSIFICATION
Hyperacutewithin 1 week after development of jaundice
Acutewithin 1-4 weeks after development of jaundice
Subacutewithin 5-12 weeks after development of jaundice
ETIOLOGY
Common Causes
Drugsacetaminophen most common (up to 40% of cases)
Viralhepatitis B > hepatitis A
Consider hepatitis E with appropriate travel history.
Uncommon Causes
Wilson diseaseKayser-Fleischer rings (uncommon); ALT
< AST; serum uric acid and phosphate low; serum, hepatic,
and urine copper high; ceruloplasmin low (5% normal)
Vascular problemsBudd-Chiari syndrome (rapid onset
ascites and/or jaundice, preexisting hypercoagulable state,
postbone marrow transplant)
Fatty liver of pregnancysecond half of pregnancy, increased
PT, mildly increased ALT and AST
Ischemiaprolonged code, severe hemorrhage
Reye syndrome
ToxinsAmanita phalloides (recent camping trip)
Malignant infiltration
Autoimmune hepatitispositive for antinuclear antibodies,
increased gamma globulins
551
Unknown
Cause is undetermined in up to 40% of cases (i.e., viral markers negative, drug levels undetectable, no other history).
EPIDEMIOLOGY
Associated with underlying conditions
Classic Presentation
Encephalopathy, jaundice, synthetic defects (flapping, yellow, and bleeding)
Common Presentation
Early
Subtle mental changes (stage 1 encephalopathy)
Mildly increased ALT and AST levels
History of drug intake is often unclear (i.e., patient does
not volunteer information without being asked).
Synthetic function may be intact or only slightly abnormal.
Late
Can include multiorgan dysfunction
COMPLICATIONS
Encephalopathy (coma), coagulopathy (bleeding), hypoalbuminemia (edema), ascites, jaundice, renal failure, increased
intracranial pressure, infection (bacterial, viral, and fungal),
hypotension, hypoglycemia
Predictors of poor outcomeage >40, cause not acetaminophen or hepatitis A or B, encephalopathy stage 3 or 4, PT
>50 seconds, bilirubin >17.5 mg/dL
Rule out treatable causes.
Hepatitis A virus IgG, IgM (HBsAg), anti-HBsAg, hepatitis B virus DNA, hepatitis C virus RNA, hepatitis E virus,
cytomegalovirus, Epstein-Barr virus, ceruloplasmin, urine
and serum copper levels, drug screen, antinuclear antibodies, and gamma globulins.
Establish baselines.
CBC, electrolytes, creatinine, BUN, uric acid, calcium,
phosphorus, AST, ALT, bilirubin, alkaline phosphatase,
552
III DISEASES
PT, PTT, fibrinogen, factor V level (indicator of shortterm synthetic function), albumin, arterial blood gases
Iron studies can be misleading.
Increased liver enzymes with no encephalopathy or synthetic defect is not fulminant liver failure.
MANAGEMENT
Transplant candidate vs. nontransplant candidate
Transplant candidacyage <65, no malignancy, no sepsis, no HIV, no active cardiac disease, good family and
social support
Spontaneous bacterial peritonitis not a contraindication.
Contact a transplant center early with questions; the center
will request age, sex, blood type, diagnosis (if known), comorbidities, current medications, past surgical history, social
history, alcohol and drug history, current treatment.
Management either while awaiting transplant or transport
or if transplant is not an option
Supportive careblood products, intubation, maintenance
of low intracranial pressure (intracranial pressure monitor,
mannitol, hyperventilation, elevation of head), prophylactic antimicrobials (amphotericin 10 mg IV and valganciclovir 900 mg IV twice daily [high mortality from
fungal and cytomegalovirus infections]), nutrition, bowel
decontamination (neomycin), IV glucose, N-acetylcysteine (consider use in all cases of fulminant hepatic failure)
Experimentalbioartificial perfusion devices, charcoal
hemoperfusion, xenoperfusion
553
III DISEASES
HIV DISEASE COMPLICATIONS
Kiran M. Bambha, M.D.
Stacey A. R. Vlahakis, M.D.
DEFINITION
Immunodeficiencythe hallmark of HIV
In 1993, the Centers for Disease Control and Prevention
described clinical AIDS that results from infection with 23
opportunistic infections (e.g., Pneumocystis carinii pneumonia) and neoplasms (e.g., Kaposi sarcoma).
Also included in this definition
HIV seropositive patients with weight loss, diarrhea,
or dementia
HIV seropositive patients who ever had a CD4 count
<200 cells/g or a CD4 percentage <14%
ETIOLOGY
AIDS is caused by the human retroviruses HIV-1 and HIV2 (HIV-1 is the more common virus in the U.S.).
The virus can infect all cells expressing the CD4 and
chemokine coreceptors, which act as entry receptors for HIV.
The CD4 helper T cell is the primary cell affected, but other
cells that may be involved include B lymphocytes,
macrophages, and glial cells.
HIV induces both qualitative and quantitative changes in
CD4 cells.
Most of the disorders caused by the virus can be explained
by one of the following three mechanisms:
Immunodeficiency as a direct result of the effect of the
virus on immune cells
Autoimmune phenomena secondary to disordered cellular or B-lymphocyte function
Neurologic impairment caused by direct effects of the virus
or, more commonly, release of cytokines and neurotoxins
by infected macrophages capable of disseminating HIV
to multiple organ systems.
555
FEATURES
HIV is transmitted by
Sexual contact with an infected person
Parenteral exposure to infected blood or blood products by
needle sharing or transfusion
Occupational exposure in health care workers
Perinatal exposure
The illness induced by the infection may be characterized by
Constitutional complaints including weight loss, sweats,
wasting
Opportunistic infections
Aggressive cancers such as Kaposi sarcoma and extranodal lymphoma
Neurologic disorders
DIAGNOSIS AND EVALUATION
Complications related to HIV may affect almost any organ
system. A useful approach is to evaluate the organ system(s)
involved.
Important measurethe patients CD4 lymphocyte count
The relation between the CD4 count and development of
certain complications and opportunistic infections is outlined in Table 1.
The major diagnoses to be considered for an HIV patient
according to organ system involved and presenting symptoms are listed in Table 2.
The diagnosis and treatment of specific disease entities
are provided in Table 3.
Prophylactic regimens for opportunistic infections in AIDS
patients are summarized in Table 4.
Current treatment of HIV infection is not discussed. For
the most current information on HIV/AIDS, the reader
should refer to the most recent literature on the subject.
556
Table 1. Relation of CD4 Cell Count to Opportunistic Infections and Other Complications
CD4 cell count
Infections
Acute retroviral syndrome, Candida vaginitis
200-500 cells/mm3
Pneumococcal & other bacterial pneumonias,

pulmonary TB, Kaposi sarcoma, herpes zoster,
thrush, cryptosporidia (self-limited), oral
hairy leukoplakia
<200 cells/mm3
Pneumocystis carinii pneumonia, toxoplasmosis,

disseminated histoplasmosis, disseminated
coccidioidomycosis, progressive multifocal
leukoencephalopathy, miliary/extrapulmonary TB
Disseminated herpes simplex, toxoplasmosis,
cryptococcosis, cryptosporidiosis, microsporidiosis, Candida esophagitis
Disseminated CMV, disseminated Mycobacterium
avium complex
<100 cells/mm3
<50 cells/mm3
Noninfectious complications
Persistent generalized lymphadenopathy,
myopathy, aseptic meningitis, Guillain-Barr
syndrome
Cervical intraepithelial neoplasia, cervical
cancer, B-cell lymphoma, Hodgkin lymphoma,
lymphocytic interstitial pneumonitis, mononeuropathy multiplex, anemia, idiopathic
thrombocytopenic purpura
Wasting, cardiomyopathy, peripheral neuropathy,
HIV-associated dementia, vacuolar myelopathy,
progressive polyradiculopathy, non-Hodgkin
lymphoma
Central nervous system lymphoma
557
CMV, cytomegalovirus.
From Bartlett JG. The Johns Hopkins Hospital 2000-2001 guide to medical care of patients with HIV infection. 9th ed. Philadelphia:
Lippincott Williams & Wilkins; 2000. p. 51-4. Used with permission.
III DISEASES
>500 cells/mm3
558
Table 2. Diagnostic Considerations for Complications in HIV According to Involved Organ System
Organ system
Sinopulmonary
Complications, findings
Potential causes
Streptococcus pneumoniae, Haemophilus influenzae,

Pseudomonas aeruginosa, Staphylococcus aureus,
Legionella pneumophilia, Klebsiella pneumoniae,
Cryptococcus, other fungi, Alternaria, CMV
Pneumonia
Consider both infectious and noninfectious causes: PCP,
TB, S. pneumoniae, H. influenzae, gram-negative rods,
Staph. aureus, Nocardia, P. aeruginosa, Legionella
(uncommon), MAC, Cryptococcus, histoplasmosis,
Candida, Aspergillus (uncommon), Coccidioides
immitis, Rhodococcus, CMV, influenza, HSV, VZV,
Kaposi sarcoma, lymphoma, lymphocytic interstitial
pneumonia, aspiration, nonspecific interstitial
pneumonitis
Radiologic abnormalities (nodules, cavitary lesions) TB, Cryptococcus, Nocardia, MAC, histoplasmosis, PCP,
Rhodococcus, Aspergillus, Kaposi sarcoma, lymphoma,
Staph. aureus (especially IV drug abusers)
Pneumothorax
PCP, aerosolized pentamidine
Sinusitis
Table 2 (continued)
Organ system
Oral cavity
Esophagus
Liver
Cholecystitis
AIDS, cholangiopathy & papillary stenosis
Potential causes
Thrush, oral hairy leukoplakia, aphthous
ulcers, CMV, HSV, Kaposi sarcoma,
gingivitis/periodontitis
559
Candida, CMV, HSV, aphthous ulcers,

Kaposi sarcoma
Medications (all antiretrovirals, sulfonamides,
imidazoles, antituberculous medications,
pentamidine, clarithromycin, ddI), mycobacterial infections, CMV, hepatitis B or C
virus, lymphoma, disseminated bacterial &
fungal infections, fatty liver due to malnutrition, ETOH
More likely to be acalculous than in non-HIV
patients
CMV, Cryptosporidium & Microsporidia have
been implicated, papillitis, isolated bile duct
stricture
III DISEASES
Biliary tree
Visible oral lesions that may or may not be
symptomatic, plaques, erythema, dysphagia,
odynophagia, bleeding gums, unpleasant taste,
dry mouth, salivary gland enlargement
(usually benign cystic enlargement)
Esophagitis, dysphagia, odynophagia, ulcers,
chest pain
Hepatitis, right upper quadrant pain, nausea,
vomiting, elevated liver enzymes with/without
symptoms, hepatomegaly, hepatic steatosis &
development of lactic acidosis may complicate
treatment with NRTIs due to mitochondrial
toxicity induced by these medications
560
Table 2 (continued)
Organ system
Pancreas
Pancreatitis, pancreatic insufficiency, nausea,

vomiting, abdominal pain
Spleen
Splenomegaly
Bowel
Enterocolitis, diarrhea (acute or chronic),

abdominal pain, anal dysplasia/squamous cell
carcinoma
Potential causes
Medications (ddI, ddC, sulfonamides, corticosteroids,
pentamidine, INH, 3TC, rifampin, erythromycin,
paromomycin), HIV, CMV, mycobacteria, toxoplasmosis, Candida, Cryptosporidium, Cryptococcus,
ETOH, hypertriglyceridemia, cholelithiasis, lymphoma,
Kaposi sarcoma
Treatment should focus on the most likely cause; may
institute pancreatic supplements as needed
Lymphoma, MAC, HIV, cirrhosis, fungal infections
(histoplasmosis, PCP)
Medication effect (including protease inhibitors),
Campylobacter jejuni, Clostridium difficile, Salmonella,
Shigella, CMV, adenovirus, calicivirus, astrovirus,
Giardia, Entamoeba histolytica, Cryptosporidium,
Isospora, Microsporidia, HIV, small-bowel overgrowth,
MAC, Cyclospora cayetanensis, idiopathic diarrhea
(diagnosis of exclusion); HPV is associated with anal
squamous neoplasia; Kaposi sarcoma or lymphoma may
involve bowel
Table 2 (continued)
Organ system
Papules, pustules, pruritus, nodules, ulcerative
lesions, vesicles, plaques, macules, petechiae,
purpura
Central nervous
system
Meningitis, encephalitis, dementia, focal

neurologic deficits, altered mental status,
paraparesis, retinitis, visual changes, headache,
myelopathy, mononeuropathy multiplex, seizures
Potential causes
561
Drug reaction (TMP-SMX, dapsone,

nevirapine, delavirdine, efavirenz), abacavir
has been associated with severe hypersensitivity reaction (fever, rash [maculopapular
or urticarial], GI symptoms, dyspnea,
arthralgias) in 2%-3% of patients, HSV,
herpes zoster, Kaposi sarcoma, bacillary
angiomatosis, nodular prurigo, cryptococcosis, Staphylococcus aureus, eosinophilic
folliculitis, molluscum contagiosum,
seborrhea (Malassezia furfur), psoriasis,
ITP, TTP, eczema
Toxoplasmosis, Cryptococcus, lymphoma, TB,
bacterial infection/abscess, Nocardia, CMV,
neurosyphilis, HSV, VZV, PML due to JC
virus, AIDS dementia complex; other causes
of mental status changes (hypoglycemia,
hyponatremia, medications, hypoxemia, other
metabolic abnormalities/nutritional deficiencies), depression
III DISEASES
Skin
562
Table 2 (continued)
Organ system
Central nervous system

(continued)
Brain imaging abnormalities (solitary vs.

multiple lesions, punctate lesions, enhancing
vs. nonenhancing lesions)
Inflammatory demyelinating polyneuropathy,
progressive polyradiculopathy, sensory
neuropathy, myopathy, mononeuropathy
multiplex
Peripheral nervous
system
Cardiac
Dilated cardiomyopathy, pericardial effusion,

pericarditis, tamponade, endocarditis, drugrelated toxicity, pulmonary hypertension,
cardiac neoplasms (including Kaposi sarcoma
& lymphoma), echocardiography may show
dilated cardiomyopathy in up to 8% of HIV
patients, may require myocardial biopsy for
diagnosis, cardiomyopathy may be treated
Potential causes
(See Table 3, Central Nervous System)
CMV, HIV, drug-induced (zidovudine, ddI, ddC, d4T),

ETOH, vitamin B12 deficiency, thyroid disorders,
syphilis, diabetes, acute & chronic inflammatory
demyelinating polyradiculoneuropathies & may be seen
in early HIV presumed due to immune dysregulation;
distal symmetric polyneuropathy may be seen in
advanced HIV (cause is uncertain); also case reports of
peripheral neuropathy presumed due to lactic acidosis
induced by NRTIs
Drug toxicity (zidovudine, NRTIs, doxorubicin,
interferon, amphotericin B, TMP-SMX, pentamidine),
HIV, other viral & fungal infections (myocarditis),
other immunologically mediated effects; causes of
pericardial effusions include Staph. aureus, TB,
myocardial infarction, endocarditis, lymphoma,
Cryptococcus, Nocardia, MAC, toxoplasmosis,
& others
Table 2 (continued)
Organ system
Cardiac
(continued)
Renal
with standard heart failure regimens if
indicated, some patients with dilated cardiomyopathy respond to HAART
HIV- or heroin-associated nephropathy; acute
tubular necrosis; rising creatinine & BUN,
electrolyte abnormalities; decreased urine
output; check urinalysis & Gram stain; check
urine electrolytes if low urine output; urine
eosinophils; renal ultrasound; correct any
reversible factors for possible prerenal,
intrinsic, postrenal causes; HIV nephropathy
may respond to HAART & prednisone taper
Potential causes
III DISEASES
563
Most common renal lesion in HIV is collapsing

focal glomerulosclerosis (may progress rapidly
to end-stage renal disease)
Renal failure in AIDS is usually multifactorial &
addressed similarly to patients without HIV:
prerenal (hypovolemia, hypotension, reduced
circulating arterial blood volume), intrinsic
(acute tubular necrosis, rhabdomyolysis, acute
interstitial nephritis, hemolytic uremic syndrome, TTP, postinfectious glomerulonephritis),
postrenal (crystalluriadue to acyclovir,
indinavir, saquinavir, ritonavir, sulfadiazine;
extrinsic or intrinsic obstruction in urinary
tract)
Medications may contribute to renal failure
(pentamidine, foscarnet, cidofovir, aminoglycosides, indinavir, contrast)
564
Table 2 (continued)
Organ system
Hematopoietic
Anemia
Neutropenia
Thrombocytopenia
Pancytopenia
Lymphatic
Gynecologic
Lymphoma (non-Hodgkin, Hodgkin)

Adenopathy
Vaginitis
Cervical dysplasia/cancer
Potential causes
Bleeding, hemolysis, iron deficiency, renal insufficiency,
infection (MAC); if none of these is causative, may
consider a trial of erythropoietin
Medications (zidovudine, ganciclovir, 3TC, ddI, d4T, foscarnet, ribavirin, flucytosine, amphotericin, sulfonamide, pyrimethamine, interferon); may treat with filgrastim (granulocyte
colony-stimulating factor) (controversial)
ITP, TTP, medication-induced thrombocytopenia
Medication effect, infiltrative process involving bone marrow
(infection, neoplasm)
Lymphoma, TB, MAC, Kaposi sarcoma, syphilis, HIV,
toxoplasmosis, histoplasmosis, pneumocytosis, acute
retroviral syndrome, isolated infection with Bartonella
henselae may cause local adenopathy
Candida, bacterial vaginosis
Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobes,
H. influenzae, enteric gram-negative rods, streptococci
HPV
CMV, cytomegalovirus; ddC, zalcitabine; ddI, didanosine; d4T, stavudine; ETOH, ethanol; HAART, highly active antiretroviral therapy; HPV, human
papillomavirus; HSV, herpes simplex virus; ITP, idiopathic thrombocytopenic purpura; MAC, Mycobacterium avium complex; NRTI, nucleoside reverse
transcriptase inhibitor; PCP, Pneumocystis carinii pneumonia; PML, progressive multifocal leukoencephalopathy; 3TC, lamivudine; TMP-SMX,
trimethoprim-sulfamethoxazole; TTP, thrombotic thrombocytopenic purpura; VZV, varicella-zoster virus.
Table 3. Diagnosis and Treatment of Specific Diseases

Condition
Sinopulmonary disease
Sinusitis
Diagnosis
Treatment
565
Frontal headache, fever, sinus

Sinus X-rays (air-fluid
congestion & pain, purulent
levels, opacification of
nasal discharge, postnasal drip; sinuses) or sinus CT/
some patients may be only
MRI scans (sinus
mildly symptomatic; chronic
mucosal thickening)
sinusitis is especially common
with CD4 <200
Appropriate antimicrobial coverage

If nonsmoker, amoxicillin 500 mg tid
If smoker, cover for Haemophilus
influenzae with amoxicillinclavulanate 500 tid or ciprofloxacin
500 bid
Recommended treatment duration
10-14 days
Refer refractory cases to ear, nose,
& throat
Common cause of pneumonia,

Chest imaging shows
acute onset, seen in all stages
lobar or bronchopneuof HIV, may be associated with monia with/without
bacteremia
pleural effusions, blood
cultures, sputum Gram
stain & culture, quellung reaction
Azithromycin 500 mg PO 1 dose,

then 250 mg qd to complete a total
of 5 days or
Clarithromycin 500 mg PO bid or
Levofloxacin 500 mg PO qd or
Amoxicillin-clavulanate 875 mg PO
bid or
2nd-Generation cephalosporin
Except where noted, recommended
treatment duration is 10-14 days;
III DISEASES
Pneumonia
Streptococcus
pneumoniae
Findings, associations*
566
Table 3 (continued)
Condition
Diagnosis
Treatment
note that antimicrobial resistance is ever

increasing, resistant strains should be treated
with newer quinolones or vancomycin
Common, acute onset, seen in
Chest imaging shows
2nd-Generation cephalosporin or fluoroquinoall stages of HIV
bronchopneumonia,
lone or macrolide (not erythromycin) or
sputum Gram stain
TMP-SMX DS 1 PO bid (note increasing
& culture
incidence of resistance to TMP-SMX)
Recommended treatment duration 10-14 days
Appropriate antimicrobial coverage for specific
Gram-negative Acute onset, usually a noChest imaging shows
rods
socomial infection or with
lobar or bronchopneuorganisms; adjust according to sensitivities;
neutropenia, prolonged antimonia; cavitary lesions; 3rd-generation cephalosporin with antimicrobial use or late-stage
sputum Gram stain
pseudomonal coverage or 4th-generation
HIV (especially
& culture
cephalosporin or extended spectrum 4thPseudomonas aeruginosa)
generation penicillin with antipseudomonal
coverage
Staphylococcus Acute onset, uncommon cause, Chest imaging shows
Adjust coverage according to sensitivities,
aureus
may be a superinfection in
bronchopneumonia,
-lactam antimicrobials for MSSA (nafcillin
setting of influenza, may be
multiple nodules, or
or 1st-generation cephalosporin), vancomycin
seen in IV drug abusers (with
cavitary lesions; blood for MRSA, recommended treatment duration
septic emboli from endocarditis) cultures, sputum Gram 10-14 days
stain & culture
Streptococcus
pneumoniae
(continued)
Haemophilus
influenzae
Table 3 (continued)
Condition
Diagnosis
May be chronic or asymptomatic, Chest imaging may

uncommon infection, seen in
show nodules or cavilate-stage HIV
tary lesions; sputum
or bronchoscopy,
Gram stain, modified
AFB stain & culture
Legionella
Acute onset, consider diagnosis

in patient in endemic region or
in setting of epidemic (may be
seen with exposure to contaminated environmental water
sources)
Aspiration
Subacute onset, suspect it in

patients with depressed mental
status, neurologic disorders, or
poor oral control
Treatment
Sulfisoxazole 2 g PO q 6 hours or
TMP-SMX 1 PO bid or
Minocycline 200 mg PO bid
Recommend treatment duration 6
months
If patient has AIDS, lifelong treatment recommended
Chest imaging shows
Azithromycin 500 mg PO 1 dose
bronchopneumonia in
then 250 mg qd or
multiple, noncontigu- Clarithromycin 500 mg PO bid or
ous segments; culture Levofloxacin 500 mg PO qd
on selective media;
Recommended treatment duration
urinary Legionella
10-14 days based on clinical
antigen
improvement
-Lactam or quinolone, include
Chest imaging shows
patchy infiltrates with- anaerobic coverage (clindamycin or
out consolidation,
metronidazole) if necessary,
usually involves depen- recommended treatment duration of
dent segments of lung
2-3 weeks depending on patients
(posterior segments of
condition & degree of aspiration
567
III DISEASES
Nocardia
568
Table 3 (continued)
Condition
Aspiration
(continued)
Diagnosis
Treatment
upper lobes, superior

segments of lower
lobes), may see necrosis & cavitation if
infection is advanced
Mycobacterium May be chronic, subacute, or
Chest imaging may show Multidrug-resistant TB is a problem; perform
tuberculosis
asymptomatic; marked
focal infiltrates, cavisensitivities on all cultures; multiple regiincreased risk in all stages of
tary lesions, hilar
mens availabletailor according to patients
HIV; mean CD4 count 200-300; adenopathy, reticular
needs; patients from areas with multidrugusually represents reactivation
infiltrates, pleural effuresistant TB need 4-drug regimen; isoniazid,
of prior infection rather than
sions; the lower &
rifampin, pyrazinamide, ethambutol are
new exposure; extrapulmonary
middle lobes may be
available drug options; rifabutin is alternative
manifestations may be present
more commonly
to rifampin; streptomycin-based therapy is
involved; perform
available; check CDC Web site for detailed
multiple induced spurecommendations on treatment of TB in
tums and/or bronchosHIV (http://www.cdc.gov/mmwr/PDF/rr/
copy; sputum AFB
rr4720.pdf); patients receiving HAART may
stain & culture, if
need adjustment of dosing of rifampin &
sputum show AFB,
other TB medications or adjustment of
must distinguish TB
dosing of HAART because of altered drug
Table 3 (continued)
Condition
Mycobacterium
tuberculosis
(continued)
Mycobacterium Chronic or asymptomatic infeckansasii

tion, uncommon, seen in latestage HIV with CD4 counts
<50
Treatment
569
III DISEASES
Mycobacterium Chronic, uncommon cause,

avium
usually seen when CD4 count
complex
<50, important to note that
MAC may be present as a
colonizer only
Diagnosis
from other mycometabolism; for patients with drugbacteria, cultures proresistant strains of TB, consult an
vide definitive identifiinfectious diseases specialist
cation, but a more rapid
identification may be obtained with DNA probes;
if TB is suspected, treat
accordingly until organism is identified
Chest imaging findings
Clarithromycin 500 mg PO bid or
may vary, sputum,
Azithromycin 600 mg PO qd +
bronchoscopy, AFB
ethambutol 15-25 mg/kg qd
stain & culture
rifabutin 300 mg PO qd
Treat indefinitely unless immune
reconstitution occurs
Chest imaging may show Isoniazid 300 mg PO qd + rifaminfiltrates, nodules,
pin 600 mg PO qd + ethambutol
cysts, cavitary lesions;
25 mg/kg qd 2 months, then
perform sputum analysis 15 mg/kg qd; treat for 15 months
with AFB stain &
All strains are resistant to pyrazinaculture
mide, recommend substituting
rifabutin for rifampin if patient is
on HAART
570
Table 3 (continued)
Condition
Pneumocystis
carinii
Subacute or chronic, most
common pulmonary infection
in HIV, CD4 count <200,
median CD4 counts with
(without) prophylaxis are 30
(130), commonly seen in
late-stage HIV
Diagnosis
Chest imaging findings
may vary: diffuse or
perihilar infiltrates in
66%, atypical infiltrates
in 30%, but chest
X-ray is negative in
5%-10% of cases;
apical infiltrates may
be present in patients
receiving aerosolized
pentamidine
Pneumothorax may
occur; pleural effusions
are uncommon; LDH
elevated in 95% of cases
but has a low specificity;
low PO2, low SaO2, low
diffusing capacity; perform induced sputum
with Wright-Giemsa
Treatment
Multiple alternative regimens available:
1. TMP-SMX DS 1 PO bid 21 days;
adverse reactions are common (rash, fever)
2. Clindamycin 300-450 mg q 6 hours +
primaquine 15-30 mg base PO qd 21 days
3. Atovaquone 750 mg PO bid with food
21 days
4. Pentamidine 4 mg/kg qd IV 21 days
(usually reserved for severe cases of PCP)
Patients with moderately severe to severe
disease (i.e., PO2 <70 mm Hg or A-a gradient
>35 mm Hg) should be given course of
steroids (prednisone 40 mg PO bid 5 days,
then 40 mg PO qd 5 days, then 20 mg PO
qd until treatment completed)
Table 3 (continued)
Condition
Pneumocystis
carinii
(continued)
Cryptococcus
Chronic, subacute, or asymptomatic; fairly common; seen

in late-stage HIV; CD4 <50;
up to 80% of patients with
cryptococcal pneumonia also
have cryptococcal meningitis
Diagnosis
Treatment
571
Treat disseminated cryptococcosis

with meningeal involvement with
amphotericin B 0.7-1.0 mg/kg qd
IV + flucytosine 100 mg/kg qd
14 days PO, then fluconazole
400-800 mg qd 10 weeks, then
maintenance therapy with fluconazole 200 mg PO qd indefinitely
Treat disseminated cryptococcosis
without meningeal involvement
with fluconazole 200-400 mg PO
qd indefinitely
See IDSA Web site (http://www.
journals.uchicago.edu/IDSA/
guidelines/) for treating cryptococcosis in HIV
III DISEASES
stain or Calcoflour
White, if negative for
PCP & suspicion is still
high, perform bronchoscopy (sensitivity ~95%)
Chest imaging shows
nodules, cavitary lesions,
or diffuse infiltrates;
sputum or bronchoscopy; stain & culture;
cryptococcal antigen
titers in serum; cryptococcal antigen titers in
bronchoalveolar lavage
fluid with titer 1:8
indicating infection; LP
should be performed to
evaluate for coexisting
meningitis
572
Table 3 (continued)
Condition
Histoplasma
capsulatum
Coccidioides
immitis
Diagnosis
Subacute or chronic, consider

Chest imaging shows
in patients living in an endemic various lesions (diffuse
area (Mississippi and Ohio
or nodular infiltrates,
river valleys), advanced HIV,
nodules, focal infilCD4 <50, disease may be
trates, cavities, hilar
disseminated at diagnosis
adenopathy), perform
sputum analysis or
bronchoscopy, stains
& cultures, stains &
cultures of bone marrow if suspicion
warrants, serum or
urine antigen may be
positive in 80%-90%
of patients
Subacute or chronic, consider
Chest imaging shows
in patients living in endemic
various lesions (diffuse
region (Southwestern U.S.),
or nodular infiltrates,
CD4 count <50
nodules, focal infiltrates, cavities, hilar
adenopathy), perform
Treatment
Treat disseminated histoplasmosis with
amphotericin B 0.7-1.0 mg/kg qd IV 14
days, followed by maintenance therapy &
lifelong suppression with itraconazole
See IDSA Web site (http://www.journals.
uchicago.edu/IDSA/guidelines/) for treating
histoplasmosis in HIV
Treat diffuse pneumonia with amphotericin B

until clear clinical improvement, then treat
with fluconazole indefinitely
Treat disseminated extrapulmonary coccidioidomycosis with/without meningitis with
fluconazole 400 mg qd
Table 3 (continued)
Condition
Coccidioides
immitis
(continued)
Candida
Diagnosis
573
sputum analysis or
bronchoscopy, stains
& cultures,
Coccidioides serology
Chronic or subacute, may cause Chest imaging rarely
bronchitis, Candida is freshows infiltrate, diagquently isolated from respirnosis requires
atory secretions but rarely
demonstrating the
causes the illness, CD4 <50
organisms in biopsy
specimen, sputum
analysis is not useful
in diagnosis
Acute or subacute illness, preChest imaging may show
disposing factors include
focal infiltrates, cavineutropenia with absolute
tary lesions; lesions
neutrophil count <500 &
seen on chest X-ray or
corticosteroids, may be seen
CT can be highly sugin advanced HIV
gestive of diagnosis;
sputum stains &
cultures may be associated with high rate of
Treatment
See the IDSA Web site (http://www.
guidelines/) for treating coccidioidomycosis in HIV
Fluconazole, amphotericin B
guidelines/) for treating candidiasis in HIV
Amphotericin B, itraconazole,
caspofungin may be used in
refractory cases
guidelines/) for treating aspergillosis in HIV
III DISEASES
Aspergillus
574
Table 3 (continued)
Condition
Aspergillus
(continued)
CMV
Influenza
Diagnosis
Treatment
false-negatives and
false-positives; most
reliable diagnosis is
with biopsy showing
invasion
Subacute or chronic, CMV is
Chest imaging may show Ganciclovir or oral valganciclovir
frequently isolated from
interstitial infiltrates,
respiratory secretions but is
most reliable diagnosis
uncommon cause of pulmonary is biopsy showing CMV
disease, CMV pneumonia may inclusions
occur in advanced HIV,
CD4 <20
Acute illness; common cause of Influenza culture or rapid Within first 48 hours of illness, consider
respiratory infection (upper
stain of respiratory
zanamivir, oseltamivir (ramantadine or
respiratory tract infection,
secretions
amantadine if influenza A only); treat any
pharyngitis, bronchitis) but
superinfection according to cause
pneumonia is not common
unless due to bacterial superinfection, may occur with any
stage of HIV
Table 3 (continued)
Condition
Varicella
Acute, varicella pneumonia

usually follows cutaneous
exanthem within 1-7 days
Kaposi
sarcoma
Chronic or asymptomatic
Diagnosis
Treatment
575
III DISEASES
Chest imaging may show Acyclovir

interstitial infiltrates
with peribronchiolar
distribution; cytology,
biopsy, or culture of
respiratory secretions/
tissue may show VZV
as intranuclear inclusions & multinucleated
giant cells
Chest imaging may show Chemotherapy for systemic disease,
interstitial, alveolar, or
radiotherapy
nodular infiltrates, hilar
adenopathy, pleural
effusions; bronchoscopy
may yield endobronchial lesion, but yields
of parenchymal lesions
may be as low as
10%-30%
576
Table 3 (continued)
Condition
Lymphoma
Chronic or asymptomatic, uncommon cause of pneumonia
Lymphocytic
interstitial
pneumonia
Subacute or chronic, CD4

<200 commonly
Diagnosis
Treatment
Chest imaging may show Chemotherapy

various lesions (interstitial, alveolar, nodular
infiltrates, cavitary
lesions, pleural
effusions, hilar
adenopathy); perform
bronchoscopy with
transbronchial biopsy;
VATS or open lung
biopsy if needed;
biopsy of extrapulmonary sites
HAART, prednisone
Chest imaging shows
diffuse reticular or focal
infiltrates; bronchoscopy with biopsy may
give diagnosis 30%-50%
of time, but may need to
perform VATS or open
lung biopsy
Table 3 (continued)
Condition
Nonspecific
interstitial
pneumonia
GI disorders
Diarrhea
Salmonella
Diagnosis
Treatment
No specific radiologic
HAART, prednisone
findings, biopsy shows
diffuse alveolar damage
with interstitial inflammatory infiltrate
consisting of macrophages & lymphocytes
Gastroenteritis or enteric fever
Blood & stool cultures,

may have fecal WBCs
Dysentery, fever, colitis
Stool cultures, fecal

WBCs
Campylobacter Watery stools or dysentery,

jejuni
may be associated with fever,
colitis
Blood & stool cultures,

may have fecal WBCs
Ciprofloxacin 500-750 mg PO bid

14 days or
TMP-SMX DS 1-2 PO bid 14
days
Ciprofloxacin 500 mg PO bid
3 days or
TMP-SMX DS 1 PO bid 3 days
Ciprofloxacin 500 mg PO bid
3-5 days or
Azithromycin 500 mg PO qd
3-5 days
577
III DISEASES
Shigella
Subacute or chronic
578
Table 3 (continued)
Condition
Clostridium
difficile
Small-bowel
overgrowth
MAC
Diagnosis
Watery stools, fever, leukocytosis, colitis, almost always

associated with antimicrobial
use (cephalosporins, clindamycin, ampicillin)
Watery stools, malabsorption,
afebrile
C. difficile toxin assay,

may have fecal
WBCs
Treatment
Metronidazole 500 mg PO tid 10-14 days or
Vancomycin 125 mg PO qid 10-14 days
Small-bowel aspirate for Doxycycline or metronidazole or amoxicillinquantitative culture,

clavulanate
hydrogen breath test,
no fecal WBCs
Small-bowel biopsy with Clarithromycin 500 mg PO bid + ethambutol
AFB stain/culture
15 mg/kg qd rifabutin 300 mg/day
Watery stools; enteritis;

commonly associated with
MAC bacteremia & fever,
abdominal pain; CD4 <50
Cryptosporidia Enteritis, profuse watery stools, Stool-modified AFB
commonly afebrile, CD4 <200 stain shows oocytes,
no fecal WBCs
Isospora
Watery stools, enteritis,
Stool AFB, no fecal
usually afebrile, CD4 <100
WBCs
No treatment is consistently effective, paromomycin may be helpful, treat symptomatically,

octreotide may be useful
TMP-SMX DS 1 PO qid 10 days, then bid
3 weeks or
Pyrimethamine 50-75 mg PO qd + folinic acid
10 mg qd 14 days
Table 3 (continued)
Condition
Microsporidia
Giardia
Entamoeba
histolytica
Diagnosis
Stool trichrome stain,

electron microscopy
or Giemsa stain of
small-bowel biopsy
Watery diarrhea, may be
Stool ova & parasite
associated with malabsorption, studies, Giardia
afebrile, enteritis, bloating,
antigen assay
flatulence, especially seen in
travelers & homosexual men
If symptomatic, may have
Stool ova & parasite
bloody diarrhea, fever, &
studies, yield of
colitis; asymptomatic carstudies may vary with
riage common, particularly in
technical expertise;
homosexual men; may be more fecal RBCs; endoscopy
frequent in travelers &
with biopsy; elevated
homosexual men
IFA titer
Watery diarrhea
Circular organisms seen
on AFB staining
Treatment
Albedazole 400-800 mg PO bid
for at least 3 weeks, best results if
combined with HAART
Metronidazole 250 mg PO tid 5
days or
Albendazole 400 mg PO qd 5 days
Metronidazole 750 mg PO tid
10 days, followed by paromomycin
500 mg PO tid 7 days or
Iodoquinol 650 mg PO tid 20 days
TMP-SMX DS 1 PO qid 10 days,

then 1 PO 3/week
579
III DISEASES
Cyclospora
cayetanensis
Watery stools, enteritis, usually
afebrile, CD4 <50
580
Table 3 (continued)
Condition
CMV
Enteric
viruses
Idiopathic
Liver disease
Seen in disseminated CMV,
fever, abdominal pain, colitis,
enteritis, may be complicated
by colonic perforation or GI
bleed, CD4 <50
Watery stools, enteritis
Watery stools, wasting,

protein-losing enteropathy
May present with nausea,
vomiting, RUQ pain, elevated
aminotransferases & alkaline
phosphatase
Diagnosis
Flexible sigmoidoscopy
or colonoscopy with
intestinal biopsy
showing CMV
inclusions
Most common causes
are adenovirus,
calciviruses, picornavirus, astrovirus
No pathogens identified, small-bowel
biopsy may show
villous atrophy
Ultrasound, CT, liver
biopsy if needed
Treatment
Ganciclovir
Symptomatic
Symptomatic, TPN if needed
Tailor treatment to cause of disorder
Table 3 (continued)
Condition
Diagnosis
Treatment
581
III DISEASES
Biliary disease
Cholangiopathy May present with nausea,
Ultrasound shows dilated Sphincterotomy may help, but
vomiting, RUQ pain, markedly ducts, ERCP shows
symptoms frequently recur;
elevated alkaline phosphapruning of terminal
endoscopic stenting
tase compared to aminotransducts & irregularities
ferases
of proximal intrahepatic
ducts, stenosis of distal
common bile duct
Oral disease
Clotrimazole PO troches or nystatin
Thrush
White plaques that are easily
Usually clinical diag(Candida)
scraped off; may present as
nosis; KOH shows
or fluconazole PO until lesions
erythematous, friable lesion;
yeast & pseudohyphae
resolve
dry mouth, bad taste in mouth
Thrush frequently relapses in absence of immune reconstitution, but
concern about maintenance therapy
is development of azole-resistant
strains of Candida
Oral hairy
Usually asymptomatic; wellUsually clinical diagno- Acyclovir, frequently recurs if not
on maintenance therapy with
leukoplakia
demarcated verrucous plaque
sis, does not rub off,
582
Table 3 (continued)
Condition
Oral hairy
leukoplakia
(continued)
Aphthous
ulcers
with white hair-like projections on lateral or inferior
aspect of tongue; associated
with Epstein-Barr virus
Painful ulcerations on mucosa
HSV
Small, painful vesicles on

erythematous base
Kaposi
sarcoma
Purple, red, black, or brown

firm nodules, especially on
hard palate
Diagnosis
does not respond to
anticandidal therapy
Exclusion of HSV,
CMV, VZV as cause
Treatment
high-dose acyclovir
Topical podophyllin 25%
Miles solution (hydrocortisone, nystatin,

tetracycline, viscous lidocaine mixture),
dexamethasone solution, topical fluocinonide
with orobase, thalidomide is experimental,
prednisone may be used for severe cases
May be clinical diagnosis Acyclovir or famciclovir or valacyclovir
in patients with history
of similar lesions,
Tzanck smear shows
multinucleate giant
cells & intranuclear
inclusions
Local therapy (laser, chemotherapy, radioBiopsy may be needed
therapy), systemic chemotherapy for extensive disease
Table 3 (continued)
Condition
Gingivitis/
periodontitis
Esophageal disease
Candida
Painful bleeding gums, cratered
ulcers, red marginal gum line,
necrosis of interdental papillae,
due to bacterial overgrowth
Usually presents as dysphagia,
odynophagia, chest pain
Usually (not invariably)
associated with thrush;
afebrile, CD4 <100, white
plaques
Diagnosis
Treatment
May require professional cleaning &
debridement; topical antiseptic
mouth rinses; severe cases may
require antimicrobials (metronidazole or clindamycin) to cover
anaerobes
583
III DISEASES
Usually clinical diagFluconazole

nosis; endoscopy shows
typical white plaques,
with microscopic exam
showing yeast
In patient with esophageal pain, it is reasonable to treat empirically
for Candida and
evaluate further if no
improvement
584
Table 3 (continued)
Condition
CMV
HSV
Aphthous
ulcers
CNS disorders
Toxoplasmosis
Diagnosis
Treatment
Often febrile; localized, severe Endoscopy shows ulcera- Ganciclovir

pain; CD4 <100; ulcerative
tions, biopsy shows
lesions
CMV inclusions
Afebrile, focal pain, vesicles
Endoscopy shows small, Acyclovir or valacyclovir or famciclovir
on erythematous base, patients confluent ulcerations;
often have coexisting vesicles
biopsy shows HSV
in the oral cavity, CD4 <100
inclusions
Afebrile, localized pain
Endoscopy, no evidence Prednisone taper, thalidomide (experimental)
of other pathogens
Headache, focal neurologic
signs, fever, lethargy, seizures,
mental status changes, CD4
usually <200
Pyrimethamine, folate, & sulfadiazine; should

Characteristic contrastenhancing lesions on
see response within 1 week (clinically) & 2
CT, with nodular or
weeks (radiographically); if not, consider
ring-enhancing strucother diagnoses
ture with mass effect;
Patients require life-long suppressive therapy
usually multiple lesions; with pyrimethamine, folate, & sulfadiazine
MRI may be more
Control cerebral edema with dexamethasone
sensitive than CT for
detecting toxoplasmosis; a positive serum
toxoplasmosis titer may
Table 3 (continued)
Condition
Toxoplasmosis
(continued)
Primary CNS
lymphoma
Headache, focal neurologic

deficits, seizures, mental
status changes, usually occurs
with CD4 <100
Diagnosis
Treatment
III DISEASES
585
be found in absence of
disease, thus cannot be
used in diagnosis;
toxoplasmosis serology
may be negative in up
to 15% of patients
with disease
CT or MRI shows
Radiotherapy may improve neurologic outcome, quality of life, &
single or multiple
contrast-enhancing
survival
lesions; may be difficult to distinguish from
toxoplasmosis based on
imaging & symptoms
alone; definitive diagnosis for focal brain
lesions may need
stereotactic biopsy;
PCR for Epstein-Barr
virus in CSF may help
make diagnosis
586
Table 3 (continued)
Condition
Non-Hodgkin
lymphoma
Progressive
multifocal
leukoencephalopathy
Diagnosis
Metastatic lymphoma to brain; Repeated LP for CSF

may present with mental status analysis, including
changes, cranial neuropathies,
cytology; bone marrow
spinal root lesions; more than
biopsy; CT of chest,
70% of cases in HIV patients
abdomen, pelvis, head
tend to be extranodal & fairly
aggressive tumors
Due to the JC virus; infection
CT may show single or
of white matter; may present
multiple confluent,
as altered mental status,
hypodense, nonenspeech, visual & gait disturhancing lesions,
bances, hemiparesis, cortical
primarily in parietoblindness, incoordination;
occipital white matter
aphasia; usually in advanced
without mass effect
HIV; CD4 <200
MRI may be superior
to CT
Definitive diagnosis
requires biopsy
PCR for JC virus may
have false-negative rate
of up to 40%-50%
Treatment
Systemic chemotherapy (CHOP or MBACOD)
For CNS involvement, therapy may include
cranial irradiation or intrathecal
chemotherapy
HAART, cidofovir (currently experimental)
Table 3 (continued)
Condition
Cryptococcal
meningitis
Due to Cryptococcus
neoformans; CD4 usually
<100; classic signs of meningitis (photophobia & neck
stiffness) are often absent;
presentation may include
malaise, fever, nausea,
vomiting, headache; less
commonly patient may have
cranial nerve palsies,
psychiatric disorder, speech
abnormalities, & seizures
Diagnosis
Treatment
587
III DISEASES
CSF India ink stain; CSF Treat disseminated cryptococcosis

cryptococcal antigen
with meningeal involvement with
titer >1:8; CSF culture
amphotericin B 0.7-1.0 mg/kg IV
positive for
qd + flucytosine 100 mg/kg qd
Cryptococcus; opening
14 days PO, then fluconazole
pressure should be
400-800 mg qd 10 weeks, then
recorded when permaintenance therapy with fluconaforming LP; usually
zole 200 mg PO qd indefinitely
no focal lesions on CT; CSF, not serum, cryptococcal antipositive cryptococcal
gen titers may be useful for
antigen titer may be
monitoring response to treatment;
noted in blood in >90% unfavorable prognostic factors
of cases
include elevated opening pressure,
altered mental status, elevated CSF
cryptococcal antigen titer, low CSF
WBC count
guidelines/) for treating cryptococcosis in HIV
588
Table 3 (continued)
Condition
CMV encephalitis
HSV encephalitis
Usually seen with CD4 <50;
often associated with CMV
involvement of other organ
systems, including adrenals
(which may present as
hyponatremia); presentation
is characterized by fairly
abrupt onset of mental status
changes, patient may be
afebrile
HSV frequently affects
temporal lobe orbitofrontal
cortex & limbic structures;
may present with fever,
focal neurologic symptoms
(especially referable to
temporal lobe), focal seizures
(especially of temporal lobe),
depressed consciousness,
personality changes, altered
mental status
Diagnosis
CT shows hydrocephalus
& periventricular or
meningeal enhancement,
perform ophthalmoscopy
to evaluate for retinitis,
CMV PCR of CSF
Treatment
Ganciclovir
Prognosis of CMV encephalitis is poor,
therapy not shown to improve survival
Most sensitive test is

Acyclovir or foscarnet or valacyclovir
detection of HSV DNA
in CSF by PCR (may be
negative during first 2448 hours after infection);
MRI of head (T2-weighted)
may show high-intensity
signal lesions in temporal
lobe
CSF with high opening pressure & mild-to-moderate
Table 3 (continued)
Condition
HSV encephalitis
(continued)
May occur with/without recent

history of characteristic
vesicular rash; depressed
consciousness, headache,
vomiting, altered mental
status, fever, seizures
Treatment
589
III DISEASES
VZV encephalitis
Diagnosis
increase in protein &

lymphocyte predominance & normal or
mildly decreased glucose; CSF viral cultures
nearly always negative
Diagnosis may also be
based on detection of
HSV antigen, HSV
DNA, or HSV replication in brain biopsy
tissue (brain biopsy
usually not needed
for diagnosis)
Lymphocyte predomiAcyclovir or foscarnet (preferred
nance in CSF; VZV
treatment for acyclovir-resistant
antibody detected by
VZV) or cidofovir
indirect immunofluorescence in CSF
in titer of 1:2; detection
of VZV DNA in CSF
590
Table 3 (continued)
Condition
VZV encephalitis
(continued)
Neurosyphilis
Due to Treponema pallidum;

presentation may vary,
including asymptomatic
infection, meningitis, tabes
dorsalis, general paresis,
meningovascular disease,
ocular disease
AIDS dementia
complex
May occur with CD4

<100; patient is generally
alert & afebrile; symptoms/
signs may include forgetfulness, difficulty concentrating,
Diagnosis
by PCR; radiologic evidence
of multifocal ischemic &
hemorrhagic infarctions of
white matter > gray
matter, often at the graywhite matter junction
Positive CSF VDRL is
diagnostic (but sensitivity
of 30%-70%), CSF may
show increased protein &
pleocytosis
Neuropsychiatric testing
may show cognitive
dysfunction; no imaging
studies are specific for
AIDS dementia (may show
Treatment
If patient with positive serum VDRL,

symptoms consistent with neurosyphilis,
& CSF profile compatible with
Treponema infection, treat presumptively
for neurosyphilis even if CSF VDRL is
negative
Treatment is aqueous penicillin G 12-24
million units qd 10 days; serum & CSF
VDRL levels & CSF fluid analysis
should be followed serially 1-2 years
High-dose zidovudine is effective; calcium
channel blockers are being investigated
Table 3 (continued)
Condition
AIDS dementia
complex
(continued)
loss of balance, leg weakness,

slowed mentation, social
withdrawal; seizures,
incontinence, tremor, &
paraparesis may occur with
advanced dementia
May present as altered mental

status, fever, cranial nerve
palsies (TB has predilection
for skull base)
Treatment
591
III DISEASES
TB
Diagnosis
cerebral atrophy,
ventricular enlargement, white matter
changes); it is diagnosis
of exclusion; perform
imaging & LP to
evaluate other causes of
neurologic change;
presence of 2-microglobulin, neopterin, &
quinolinate in CSF may
correlate with presence
of AIDS dementia
complex
CT may show intracere- See the CDC Web site (http://www.
bral enhancing lesions
cdc.gov/mmwr/PDF/rr/rr4720.pdf)
(tuberculous abscess,
for treating TB in HIV
tuberculomas) in 50%70% of cases, brain
biopsy may be needed
592
Table 3 (continued)
Condition
TB (continued)
HIV meningitis
Common in early HIV

infection, may present with
fever & headache
Diagnosis
to idenfity the mass; obtain chest X-ray, positive
TB culture from any site
suggests the diagnosis,
CSF culture may be positive in 20% of cases
HAART
No focal abnormalities on
CT, CSF has a mild
mononuclear pleocytosis
(<200 cells/mm3) &
elevated protein; all
cultures are negative for
other pathogens
Note: HIV is associated
with mild mononuclear
pleocytosis (<100
cells/mm3) with/without
elevated protein even in
absence of neurologic
symptoms; this may confound interpretation of
CSF results in HIV patients
Treatment
Table 3 (continued)
Condition
HIV myelopathy
Retinitis
Diagnosis
MRI or CT of spinal
cord & LP to evaluate
for potentially treatable
causes of myelopathy
Treatment
No effective treatment for AIDSassociated vacuolar myelopathy,
symptomatic relief may be
achieved with antispasticity
agents & physical therapy
Ophthalmoscopy may
IV foscarnet or IV ganciclovir or
show cotton-wool spots IV cidofovir; life-long maintenance
without associated
therapy with foscarnet, ganciclovir,
hemorrhage or exudate
or cidofovir is recommended for
in HIV retinitis (lesions patients without immune reconmay remit spontanestitution; ganciclovir implants are
ously & are benign);
an option but provide no protection
may show perivascular
against systemic CMV & no
hemorrhage & fluffy
protection for uninvolved eye
593
III DISEASES
Slowly progressive gait disturtance, sensory changes in

lower extremities, sphincter
dysfunction, hyperreflexia,
spastic paraparesis
Causes of myelopathy may
include vacuolar myelopathy
(most common cause in
AIDS patients), toxoplasmosis, lymphoma, VZV, HSV,
CMV, vitamin B12 deficiency
May be due to CMV or HIV
(less commonly, HSV,
syphilis, fungal infections,
herpes zoster, toxoplasmosis);
with CMV retinitis, patients
usually asymptomatic until
lesions involve fovea, optic
nerve, or cause retinal detachment; patients may complain
594
Table 3 (continued)
Condition
Retinitis
(continued)
PNS disorders
Inflammatory
demyelinating
polyneuropathies
Distal symmetric
polyneuropathy
of floaters, blurry vision,
visual field deficits; CMV
retinitis not generally
associated with pain or light
sensitivity
May be acute or chronic; tend
to occur early in HIV; acute
illness resembles GuillainBarr syndrome; patients may
present with progressive
weakness, areflexia, sensory
signs; thought to be
autoimmune-related process
Most common polyneuropathy
in HIV, incidence increases
with advanced HIV; cause
not known; may present with
symmetric paresthesias, pain,
numbness, dysesthesia of
Diagnosis
Treatment
exudates, opaque retinal

lesions
Variable clinical course, but most patients

Mild mononuclear pleocytosis & elevated protein
improve; may respond to corticosteroids,
in CSF (nonspecific finding plasmapheresis, IV immunoglobulin
in HIV), EMG may show
demyelination & axon loss
Must rule out other causes

of distal symmetric polyneuropathy, including
vitamin B6 & B12
deficiencies, diabetes,
alcoholism, medications
Treatment is symptomatic relief with

tricyclic antidepressants, anticonvulsants,
analgesics, or topical capsaicin; antiretroviral therapy has no efficacy
If medication is suspected cause, a drug
holiday may benefit
Table 3 (continued)
feet; decreased or absent
ankle reflexes; decreased
sensation to pain & vibration
in lower limbs; upper limb
involvement less common &
may occur later in disease
Likely due to CMV infection
of nerve roots; findings
include lower limb & sacral
paresthesias or pain, rapidly
progressive flaccid paralysis,
areflexia, sphincter disturbances, urinary retention,
sensory loss; less common
causes are neurosyphilis,
leptomeningeal lymphoma,
TB
Sensory & motor deficits in
distribution of multiple spinal,
peripheral, cranial nerves
(may include facial or
Progressive
polyradiculopathy
Mononeuropathy
multiplex
Diagnosis
Treatment
(vincristine, ddI, ddC,

d4T); EMG may show
predominant axonal
loss with demyelination
CSF shows marked
pleocytosis with predominance of PMNs;
CMV identified in
culture in ~50% of
cases
595
Nonspecific CSF
findings (pleocytosis,
elevated protein);
EMG may show axonal
Ganciclovir or foscarnet; it is
important to treat early in disease
course to prevent irreversible nerve
root damage
III DISEASES
Condition
Distal symmetric
polyneuropathy
(continued)
596
Table 3 (continued)
Condition
Mononeuropathy
multiplex
(continued)
laryngeal palsy, wrist or foot

drop); symptoms may resolve
spontaneously in early HIV
but progress rapidly to
quadraparesis in late HIV,
especially if CD4 <50
Most common causes are
presumed direct HIV-virallyinduced myopathy (may occur
at all stages of disease) &
zidovudine-associated
myopathy; may present with
proximal muscle weakness
(especially thighs), myalgia,
weight loss
Myopathy
Diagnosis
Treatment
neuropathy; sometimes
nerve biopsy shows
necrosis
HIV-associated myopathy may respond to

HIV-associated myopathy:
mild to moderate CK
corticosteroids
elevation, myopathic EMG Zidovudine-associated myopathy may,
abnormalities, up to 50%
but not always, respond to drug
may have nerve conduction
withdrawal
abnormalities
Zidovudine-associated
myopathy: muscle tenderness & weakness may be
preceded by increased CK;
muscle biopsy may show
ragged-red fibers (mitochondrial dysfunction)
Table 3 (continued)
Condition
Dermatologic disorders
Eosinophilic
folliculitis
Kaposi sarcoma
Diagnosis
Treatment
Idiopathic, pruritic, edematous

follicular papules & pustules
usually on trunk or face; seen
in advanced HIV; CD4
<100-200
III DISEASES
597
Biopsy shows perifolAntihistamines, topical corticolicular & perivascular

steroids, or permethrin cream;
infiltrates with eosinoprednisone may resolve folliculitis
phils, no evidence of
but recurrence is common after
other pathogenic
treatment cessation; isotretinoin
organisms, may be
associated with
peripheral eosinophilia
May respond to local therapy
Multisystem vascular neoplasia; Skin biopsy needed for
human herpesvirus 8 is
diagnosis; may be
(radiotherapy, cryosurgery, laser
implicated; may present as
confused with bacillary
surgery); intralesional chemoviolaceous, red, pink, brown,
angiomatosis; approxitherapy with vincristine and/or
or black macules, papules,
mately 40% of patients
bleomycin; systemic chemotherapy
plaques, or nodules; lesions
with dermatologic
for extensive mucocutaneous
may have greenish hemoKaposi sarcoma develop disease with visceral involvement
siderin halo; Kaposi sarcoma
visceral disease (GI,
may cause bulky lymphedema; pulmonary)
distribution is widespread,
including oral lesions, common
on hard palate
598
Table 3 (continued)
Condition
Bacillary angiomatosis
Herpes simplex
virus
Diagnosis
Treatment
Due to Bartonella henselae or

Biopsy showing Bartonella Avoid contact with cats; treat with erythroB. quintana; usually seen in
on silver stain
mycin or doxycycline or ciprofloxacin
or azithromycin; may benefit from
more advanced HIV, CD4
maintenance therapy if relapse occurs
<200; red or violaceous, firm
papules or nodules; may
resemble Kaposi sarcoma;
infection may spread
hematologically & involve
liver (peliosis hepatis) or
spleen (parenchymal bacillary
peliosis)
Grouped vesicles or erosions
Diagnosis based on clinical Acyclovir; if no response, may require
higher doses of acyclovir or foscarnet (if
on erythematous base; painful; appearance & possible
may be oral, genital, perihistory of recurring lesions; acyclovir-resistant strain suspected)
rectal or generalized disease;
Tzanck smear, cultures,
with increasing immunoantigen detection, or PCR
compromise, lesions may be
shows HSV
more severe with marked
ulceration & erosions
Table 3 (continued)
Condition
Vesicles on erythematous base
may progress to crusting
lesions; usually has dermatomal distribution; painful;
disseminated disease in some
patients
Molluscum
contagiosum
Viral infection; pearly white

or skin-colored, round or
oval umbilicated papules or
nodules; usually asymptomatic; hundreds of lesions
may occur in HIV patients;
may be on face, neck, trunk,
or anogenital regions;
severity may increase with
increasing immunodeficiency
Diagnosis
Treatment
Usually based on clinical Acyclovir PO or IV depending on

findings; Tzanck smear
disease severity
shows giant & multinucleated cells (as in
HSV); antigen detection; VZV serology
shows rising titers;
viral culture (difficult)
Curettage, cryosurgery, electrodesUsually clinical diagsication, or laser ablation
nosis; may require
biopsy to distinguish
from other nodular
lesions
599
III DISEASES
Herpes zoster
600
Table 3 (continued)
Condition
Diagnosis
Staphylococcus
aureus
Most common cutaneous bacterial infection in HIV; may

present as folliculitis,
furuncles, carbuncles;
lesions may be pruritic;
localized infection may
progress to bacteremia or
disseminated infection
Warts may range from papules
to cauliflower-like masses on
anogenital or oral mucosa or
skin; lesions may be extensive,
difficult to treat in advanced
HIV; associated with squamous cell carcinoma of
cervix, penis, vulva, perineum, anus
Causes include Trichophyton,
Microsporum, Epidermophyton;
infection may be extensive,
Gram-positive cocci on
microscopy; culture
positive for S. aureus
Dicloxacillin or cephalexin or other

penicillinase-resistant antistaphylococcal
agents
Usually clinical diagnosis,

biopsy if necessary
Cryosurgery, podofilox, podophyllin,

trichloroacetic acid, electrodessication
Microscopy, KOH preparation, Wood lamp, fungal

cultures
Topical or systemic antifungal agents
Human
papillomavirus
Dermatophytosis
Treatment
Table 3 (continued)
Condition
Dermatophytosis
(continued)
Drug reactions
Diagnosis
Treatment
601
III DISEASES
Syphilis
difficult to treat in HIV;

proximal white subungual
onychomycosis is common
presentation of T. rubrum tinea
unguium in HIV
Rashes may be erythematous,
Diagnosis confirmed by Discontinue offending drug
papular, or pruritic; less
resolution of rash after
common are urticaria,
offending drug
erythema multiforme, photodiscontinued
sensitivity; common offending
drugs are TMP-SMX, dapsone,
nevirapine, delaviridine,
efavirenz
Primary: painless chancre
Dark field exam, direct
Penicillin
usually in genital region
fluorescent antibody
Secondary: pink macules or
test, serologic testing
pink or brown-red papules;
for VDRL, rapid plasma
condyloma lata in moist body
reagin, FTA-ABS
regions; may have papulosquamous lesions
602
Table 3 (continued)
Condition
Syphilis (continued) Tertiary: brown, firm plaques

& nodules with/without
scales or ulceration;
gummarubbery lump
that may ulcerate
Histoplasmosis
Erythematous, necrotic or
hyperkeratotic papules or
nodules; macules; folliculitis;
pustules; ulcers; lesions may
be widely distributed; mucous
membranes are commonly
involved; disseminated
disease may be associated
with lymphadenopathy &
hepatosplenomegaly
Cryptococcosis
Papules or nodules; may
resemble molluscum
contagiosum; may also
present as vesicles, pustules,
cellulites, ulcers; lesions usually on face & scalp in HIV
Diagnosis
Treatment
Biopsy shows Histoplasma

capsulatum; culture
Treat disseminated disease with amphotericin B 0.7-1.0 mg/kg IV qd 14 days,

followed by maintenance therapy & lifelong suppression with itraconazole
journals.uchicago.edu/IDSA/guidelines/)
for treating histoplasmosis in HIV
Skin biopsy, cultures
Treat disseminated disease with meningeal

involvement with amphotericin B 0.7-1.0
mg/kg IV qd + flucytosine 100 mg/kg PO
qd 14 days, then fluconazole 400-800
mg qd 10 weeks, then maintenance
therapy with fluconazole 200 mg PO qd
indefinitely
Table 3 (continued)
Condition
Diagnosis
Treatment
Treat disseminated disease without

meningeal involvement with
fluconazole 200-400 mg PO qd
indefinitely
Coccidioidomycosis May initially present as papule Detection of Coccidiodes Treat disseminated extrapulmonary
with evolution to pustules,
immitis in skin biopsy
coccidioidomycosis with/without
plaques, nodules, ulcers,
meningitis with fluconazole 400
abscesses; usually involves
mg qd
central face (especially
nasolabial folds)
guidelines/) for treating coccidioidomycosis in HIV
Blastomycosis
Initial lesion may be inflamMicroscopy; detection of Treat with amphotericin B 0.7-1.0
matory nodule that grows &
Blastomyces antigen or
mg/kg IV qd for total dose of 1.5ulcerates; SQ nodule; pustules; antibody; culture
2.5 g, continue suppressive therapy
verrucous, crusted plaques
with itraconazole 200-400 mg qd,
with well-demarcated borders
consider fluconazole 800 mg/day
for suppression if CNS disease
present
Cryptococcosis
(continued)
III DISEASES
603
604
Table 3 (continued)
Condition
Diagnosis
Blastomycosis
(continued)
Psoriasis
Seborrheic
dermatitis
Well-demarcated plaques with

silvery scale, propensity for
extensor surfaces, may be
associated with nail pitting
or arthritis
May vary from fine white
scales without erythema to
plaques & patches of
erythema with yellow,
greasy scale; may be found
on scalp, face, chest, upper
back; pruritis
Usually clinical diagnosis
Usually clinical diagnosis
Treatment
See the IDSA Web site (http://www.journals.
uchicago.edu/IDSA/guidelines/) for
treating blastomycosis in HIV
Topical corticosteroids; phototherapy (may
be poorly tolerated due to photosensitivity
of some HIV patients); retinoids; tar
preparations
Topical corticosteroids; UV radiation;
ketoconazole cream or shampoo
AFB, acid-fast bacillus; bid, twice daily; CNS, central nervous system; CMV, cytomegalovirus; ddC, zalcitabine; ddI, didanosine; d4T, stavudine; ERCP,
endoscopic retrograde cholangiopancreatography; FTA-ABS, fluorescent treponemal antibody absorption; GI, gastrointestinal; HAART, highly active
antiretroviral therapy; HSV, herpes simplex virus; IDSA, Infectious Diseases Society of America; IFA, immunofluorescent antibody; LP, lumbar puncture; MAC, Mycobacterium avium complex; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus;
PCP, Pneumocystis carinii pneumonia; PCR, polymerase chain reaction; PNS, peripheral nervous system; q, every; qd, daily; qid, four times daily; RUQ,
right upper quadrant; tid, three times daily; TMP-SMX, trimethoprim-sulfamethoxazole; TPN, total parenteral nutrition; VATS, video-assisted thoracic
surgery; VZV, varicella-zoster virus.
*CD4 counts are cells/mm3.
Table 4. Prophylaxis for Opportunistic Infections

Disease
TB
Pneumocystis carinii
pneumonia
Indications
Positive PPD (5 mm induration),
history of prior positive PPD
without INH prophylaxis,
high-risk exposure
Prior bout; CD4 <200 cells/mm3;
thrush; FUO
CD4 <100 cells/mm3 with

presence of IgG
Mycobacterium avium
complex
CD4 <50 cells/mm3
Comments
TMP-SMX 1 DS qd or
May be discontinued if immuno1 DS 3/week or one
logic reconstitution is achieved,
SS qd or
with CD4 >200 cells/mm3 for
Dapsone 200 mg PO
3-6 months
qd or
Aerosolized pentamidine 300 mg q 3 weeks
TMP-SMX 1 DS qd
May be discontinued if immunologic reconstitution is achieved,
with CD4 >100 cells/mm3 for
3-6 months
Azithromycin 1,200 mg May be discontinued if immunoweekly or clarithromy- logic reconstitution is achieved,
cin 500 mg bid
with a CD4 >100 cells/mm3 for
3-6 months
605
III DISEASES
Toxoplasmosis
Regimen
INH 300 mg qd, with
pyridoxine 50 mg qd
for 9 months
606
Table 4 (continued)
Disease
Indications
Regimen
Varicella
Exposure to chickenpox or zoster

in person with no history of
either or negative VZV antibody
Streptococcus
pneumoniae
Influenza
All patients
Varicella-zoster immunoglobulin 625 units IM

given within 96 hours of
exposure
Pneumococcal vaccine
All patients
Influenza vaccine
Hepatitis A
For patients with antibody to

HCV, test for HAV; if anti-HAV
negative, administer HAV
vaccine
All negative anti-HBs & anti-HBc
patients
HAV vaccine 2 doses
Hepatitis B
CMV
HBV vaccine 3 doses
Comments
May have a suboptimal response in

patients with CD4 <200 cells/mm3
No definitive evidence supporting its
utility; has been associated with a
transient elevation in HIV viral load in
patients with CD4 <200 cells/mm3
May require booster dose if no response to

initial 3 doses
Prophylaxis not generally recommended;
no clear guidelines or proven efficacy;
concern over promotion of drug-resistant
strains
Table 4 (continued)
Disease
Indications
Regimen
Candida
Cryptococcosis
Histoplasmosis
CD4 <100 cells/mm3 in patient

living in endemic area & at
high risk for exposure to
histoplasmosis
Coccidioidomycosis
Neutropenia
Absolute neutrophil count

<500 cells/mL
Itraconazole 200 mg qd
Comments
Prophylaxis not generally
recommended
No evidence of survival benefit
with prophylaxis
Effective (not much supporting
data)
bid, twice daily; CMV, cytomegalovirus; FUO, fever of unknown origin; HAV, hepatitis A virus; HBc, hepatitis B core; HBs, hepatitis B surface; HCV, hepatitis C virus; PPD, purified protein derivative (tuberculin); q, every; qd, daily.
Data from the Practice Guidelines from the Infectious Diseases Society of America. [cited 2005 Oct 7]. Available from: http://www.journals.uchicago.edu/IDSA/guidelines and modified from Bartlett JG. The Johns Hopkins Hospital 2000-2001 guide to medical care of patients
with HIV infection. 9th ed. Philadelphia: Lippincott Williams & Wilkins; 2000. p. 51-4. Used with permission.
607
III DISEASES
Prophylaxisefficacy unknown &

not routinely recommended
Prophylaxis with filgastrim
(granulocyte colony-stimulating
factor) not routinely recommended
III DISEASES
HYPERTENSIVE CRISIS
Alexander Schirger, M.D.
DEFINITION
Hypertensive crisisacute, severe increase in blood pressure,
with or without end-organ damage, that occurs in a setting in
which rapid control is necessary: coronary artery disease,
aortic dissection, bleeding intracranial aneurysm, postoperative state, or heart failure
CLASSIFICATION
Hypertensive Emergency
Increased blood pressure to systolic pressure >210 mm Hg
and/or diastolic pressure >130 mm Hg causing symptoms
of severe target-organ impairment: headache, papilledema
and blurred vision, acute renal failure, acute coronary syndromes, pulmonary edema, encephalopathy, aortic dissection
Hypertensive Urgency
Sudden increase in blood pressure, with systolic pressure
>180 mm Hg and/or diastolic pressure 130 mm Hg, without overt evidence of end-organ damage but in a clinical
setting in which it is urgent to prevent progression to hypertensive emergency
Malignant Hypertension
Hypertensive urgency characterized by rapidly progressive
vasospastic disorder with increased peripheral resistance;
cerebral vessel dilatation; high plasma levels of renin,
angiotensin, and aldosterone; generalized arteriolar fibrinoid
necrosis; and target-organ damage
Special abbreviation used in this chapter: ACE, angiotensin-converting enzyme.

609
ETIOLOGY
The causes of hypertensive crisis are listed in Table 1.
EPIDEMIOLOGY
Of all patients with hypertension, <1% develop malignant
hypertension during the illness, whereas 2%-7% develop
accelerated hypertension.
Blacks are more susceptible than whites and males more
than females.
Increased risk is between ages 40 and 60.
Central nervous systemheadache, confusion, convulsions,
stupor, coma; generally referred to as hypertensive
encephalopathy
Cardiovascularacute coronary syndromes, aortic dissection,
flash pulmonary edema
Renaloliguria, microscopic hematuria, acute renal failure
Visualpapilledema, transient blindness (reversible with
adequate decrease in blood pressure), retinal hemorrhages and
exudates
Acute evaluation should include a focused physical exam to
look for the following:
Table 1. Causes of Hypertensive Crisis

Neglected or inappropriately treated essential hypertension
Abrupt discontinuation of antihypertensive medications (usually blockers & clonidine) leading to rebound hypertension
Renal artery stenosis
Coarctation of the aorta
Use of MAO inhibitors & subsequent ingestion of tyraminecontaining foods or Chianti wine
Intracerebral or subarachnoid hemorrhage
Pheochromocytoma crisis
Collagen vascular diseases, especially systemic sclerosis
Glomerulopathies
Acute head injury or stroke
Eclampsia
MAO, monoamine oxidase.
610
III DISEASES
New third heart sound (acute or worsened congestive heart
failure)
New aortic regurgitation murmur (aortic dissection)
Wet rales and orthopnea (flash pulmonary edema)
Focal neurologic signs (hemorrhagic stroke, encephalopathy)
Papilledema (defines malignant hypertension)
Additional tests should include
ECGischemic changes and left ventricular hypertrophy
(poor prognostic sign)
Chest X-rayheart size, aortic dilatation, pulmonary
venous hypertension
Urinalysismicrohematuria, RBC casts, proteinuria
Creatinine, BUN, glucose, potassium, and sodium
The above tests are diagnostic for end-organ damage.
Evaluation of the cause should be deferred until after blood
pressure is stable.
Further testing should include
Renal artery ultrasoundabnormal Doppler flow patterns
to suggest renal artery stenosis
If equivocal, consider magnetic resonance angiography or angiography.
Urinary metanephrinesscreening for increased catecholamine production in pheochromocytoma
If abnormal, confirm with 24-hour urinary catecholamines.
Aldosterone-to-renin ratio
A ratio >20 should alert to hyperaldosteronism (patients
may have normal serum potassium levels while receiving treatment with angiotensin-converting enzyme
[ACE] inhibitors).
MANAGEMENT
Hypertensive Emergencies
Decrease in mean arterial pressure by 25% within 2 hours,
and then over 6 hours further decrease to systolic pressure
160 mm Hg and diastolic pressure <100 mm Hg. The major
goal is to halt progressive organ damage.
In acute aortic dissection, the goal is to decrease systolic
611
pressure to 120 mm Hg within 20 minutes; nitroprusside

and labetolol should be used (see below).
Drug of choice is sodium nitroprusside given in ICU with
blood pressure monitoring through an arterial catheter.
Initial dose is 0.5-10.0 g/kg per minute, titrated to a maximal dose of 500 g/kg per hour.
Monitor thiocyanate levels every 48 hours, discontinue if
blood level is >12 mg/dL
If toxicity develops, give sodium nitrate or hydroxocobalamin.
Labetalol (especially in postoperative hypertension and pregnancy)IV miniboluses of 20-80 mg every 5-10 minutes
or at an infusion of 0.5-2 mg/minute
Nitroglycerin (especially in acute congestive heart failure
and coronary syndromes)infused IV at 5-100 g/kg per
minute.
Esmolol (useful in setting of tachyarrhythmias, migraine,
acute coronary syndromes) 500 g/kg IV bolus, then 25-100
g/kg per minute
Nicardipine (calcium channel blocker, useful in COPD
patients) 5-15 mg/h IV infusion
Fenoldopam (dopamine D1 and 2-agonist) 0.25-1.6 g/kg
per minute
Hypertensive Urgencies
Without evidence of end-organ damage, immediate control
of blood pressure is seldom needed, but control should be
obtained within 12-24 hours with blood pressure <160/100
mm Hg.
Sublingual nifedipine is detrimental. Do not use!
Addition of furosemide should be tried if patient has difficultto-control hypertension.
ACE inhibitors can be given safely to patients with chronic
renal insufficiency and creatinine level as high as 3 mg/dL
who do not have bilateral renal artery stenosis. Follow creatinine and potassium levels. Discontinue ACE inhibitors
if creatinine increases more than 1.0 mg/dL.
Amlodipine, -blockers, and reserpine are safe and useful
drugs.
Clonidine or labetalol PO can be used for a more gradual
decrease to a target diastolic pressure of 95 mm Hg.
612
III DISEASES
-Methyldopa and hydralazine are the drugs of choice for

hypertensive crisis of pregnancy.
If fluid overload state exists, loop diuretics should be considered for cautious use. Monitor both by chemical and
hemodynamic parameters.
613
III DISEASES
INFECTIVE ENDOCARDITIS
Axel Pflueger, M.D.
Walter R. Wilson, M.D.
DEFINITION
Infective endocarditisresults from infection primarily of
valvular endocardium and occasionally mural endocardium
CLASSIFICATION AND ETIOLOGY
Endocarditis can be classified according to
Microorganisms involved (Table 1)
Type of valve affected (native vs. prosthetic)
Clinical course (acute vs. subacute)
EPIDEMIOLOGY
Incidence/prevalence in U.S.1.7-4.2/100,000 population;
0.32-1.3/1,000 hospital admissions
Predominant ageall ages, increased incidence among
elderly patients (>70 years)
Predominant sex
Maleaortic valve
Femalemitral valve
Signs and Symptoms
Generally due to cytokine release, microemboli, congestive
heart failure, and other organ involvement
Look for
Fever
May be high, low, or absent
May be only symptom in prosthetic valve endocarditis
Heart murmur
Special abbreviations used in this chapter: TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
615
616
Table 1. Classification of Infective Endocarditis

Class
Course/comments
Underlying cardiac disease
Acute
Aggressive
May or may not have

preexisting valve disease
Subacute
Indolent
Structural valve disease
Intravenous drug
abusers
Aggressive
Early prosthetic
valve
Late prosthetic valve
60 days after valve

implant
>60 days after valve
implant
5%-10% patients on
antibiotics
Tricuspid valve (most

common), may involve
left-sided valves
Prosthesis
Culture-negative
Prosthesis
Organism
Staphylococcus aureus, group B
streptococci, Streptococcus pneumoniae, Neisseria
gonorrhoeae
Viridans streptococci, enterococci, Streptococcus
bovis, HACEK group
Staphylococcus aureus, Pseudomonas aeruginosa or
other gram-negative bacilli, Candida species
Staphylococcus epidermidis, Staphylococcus aureus,
gram-negative bacilli, Candida, Aspergillus species
Viridans streptococci, Stapylococcus epidermidis,
enterococci
Bartonella quintana (homeless people), Brucella,
fungi, Coxiella burnetii (Q fever), Chlamydia
trachomatis, Chlamydia psittaci, Tropheryma
whippelii
HACEK, Haemophilus parainfluenzae, H. aphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and
Kingella kingae.
III DISEASES
Roth spotslymphocytes surrounded by edema and hemorrhage in nerve fiber layer of retina
Osler nodessmall, tender, purplish erythematous skin
lesions from infected microemboli or hypersensitivity
reaction in pads of fingers or toes, in palms of hands or
soles of feet
Janeway lesionsmacular raised, nontender hemorrhagic
lesions in palms of hands and soles of feet
Splenomegaly
Signs of congestive heart failurechest pain, shortness
of breath, neck vein distension, gallops, rales, cardiac
arrhythmia
Symptoms related to embolizationstroke, splenic pain,
coronary artery embolism
Symptoms of intracranial mycotic aneurysm
Other features are listed in Table 2.
Complications
Congestive heart failure and neurologic embolic events have
the greatest influence on prognosis.
The complications are listed in Table 3.
Lab Findings
Positive blood cultures
Table 2. Additional Signs and Symptoms of Infective

Endocarditis
Pallor
Pleural friction rub (from
pulmonary emboli)
Night sweats, chilly sensation
Malaise, myalgia, joint pain
Back pain (may be severe)
Anorexia, weight loss
Stiff neck
Delirium, headache
Cough
Paralysis, hemiparesis, aphasia
Numbness, muscle weakness
Cold extremity with pain
(embolism)
Bloody urine (may be gross or
microscopic)
Bloody sputum (from septic
pulmonary emboli)
617
Table 3. Complications of Infective Endocarditis

Ruptured valve
Sinus of Valsalva aneurysm
Aortic root abscess
Myocardial abscess
Pericarditis
Cardiac arrhythmia
(conduction defects)
Meningitis
Cerebral emboli
Brain abscess
Ruptured mycotic aneurysm
(intracranial hemorrhage)
Septic pulmonary infarcts
Splenic infarcts
Arterial emboli and infarcts
Arthritis
Myositis
Glomerulonephritis
Acute renal failure
Mesenteric infarct
Leukocytosis in acute endocarditis

Anemia in subacute endocarditis
Increase in ESR and C-reactive protein
Presence of valvular vegitations on echocardiography
Decreased C3, C4, CH50 in subacute endocarditis
Hematuria (microscopic or macroscopic)
Rheumatoid factor in subacute endocarditis
Serologic tests (IgG, IgA) for Chlamydia, Q fever (Coxiella),
Brucella, and Bartonella may be useful in culture-negative endocarditis.
Lab Result Variations

Antibiotics may make blood cultures falsely negative.
Endocarditis caused by Aspergillus, Chlamydia trachomatis,
C. psittaci, Coxiella burnetii, Tropheryma whippelii, Bartonella
species may be associated with negative blood cultures.
Prolonged incubation of blood cultures is needed in endocarditis caused by fastidious organisms, e.g., HACEK group
(Haemophilus, Actinobacillus, Cardiobacterium, Eikenella,
Kingella), Abiotrophia species, nutritionally variant
Streptococcus viridans, Brucella species.
Pathology Findings
Vegetations consist of platelets, fibrin, and colonies of
microorganisms.
Destruction of valve endocardium, perforation of valve
leaflets, rupture of chordae tendineae, myocardial abscesses,
rupture of sinus of Valsalva
618
III DISEASES
Pericarditis may occur.

Emboli and/or infarction may be found in various body
organs, as may abscesses and microabscesses.
Kidneys may show embolic and/or immune-complex
glomerulonephritis.
DIAGNOSTIC PROCEDURES
Echocardiography
For vegetations, abscess, new prosthetic valve dehiscence,
new regurgitation
Transthoracic echocardiography (TTE)
98% specificity, <60% sensitivity
Inadequate 20% of time if obesity, prosthetic valves,
COPD, chest wall deformity
Transesophageal echocardiography (TEE)
94% specificity, 70%-100% sensitivity
Does not require antibiotic prophylaxis
TEE is preferred with prosthetic valve endocarditis or
Staphylococcus aureus infection
When TTE and TEE are negative, negative predictive
value is 95%.
Very Rarely Indicated
Cardiac catheterization may be indicated to ascertain degree
of valvular damage.
Aortic root injection may be useful when aortic root abscess
or rupture of sinus of Valsalva is suspected.
Pulmonary Ventilation Perfusion Scan

May be useful in right-sided endocarditis
Axial CT
May be useful in locating metastatic abscesses
Duke Criteria for Diagnosis

The criteria are listed in Table 4.
Diagnosis requires two major criteria, or one major and three
minor criteria, or five minor criteria.
619
Table 4. Duke Criteria for Diagnosis of Infective

Endocarditis
Major criteria
1. Positive blood culture
Typical microorganism for infective endocarditis from 2
separate blood culturesviridans streptococci,
Streptococcus bovis, HACEK group, or communityacquired Staphylococcus aureus or enterococci, in the
absence of a primary focus or
Persistently positive blood culturedefined as recovery of a
microorganism consistent with infective endocarditis from
a) blood cultures drawn more than 12 hours apart or b) all
of 3 or a majority of 4 or more separate blood cultures, with
first and last drawn at least 1 hour apart
2. Evidence of endocardial involvement
Positive echocardiogram
Oscillating intracardiac mass on valve or supporting
structures, in the path of regurgitant jets, or on
implanted material and in the absence of an alternative
anatomic explanation or
Abscess or
New partial dehiscence of prosthetic valve
New valvular regurgitation (worsening or change in preexisting murmur not sufficient)
3. Positive serologic tests for Brucella, Bartonella, or Coxiella
Minor criteria
1. Predispositionpredisposing heart condition or IV drug use
2. Fever 38.0C (100.4F)
3. Vascular phenomenamajor arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions
4. Immunologic phenomenaglomerulonephritis, Osler nodes,
Roth spots, rheumatoid factor
5. Microbiologic evidencepositive blood culture, but not meeting
major criterion as noted above or serologic evidence of active
infection with organism consistent with infective endocarditis
6. Echocardiogramconsistent with infective endocarditis but not
meeting major criterion as noted above
7. C-reactive protein, ESR increased
HACEK (see Table 1).
620
III DISEASES
MANAGEMENT
General Measures
Initial hospitalized care
Intensive care may be needed for critically ill patients.
Outpatient home IV antibiotic therapy may be used for
selected patients who are stable and reliable.
Blood culturestwo sets at three different times (12 hours
apart)
CBC, serum creatinine, BUN, electrolytes, ESR, rheumatoid factor, urinalysis, C3, C4, CH50, ECG, chest X-ray
Start antibiotics (see below)
Consider indwelling central venous catheter line for IV antibiotics.
Keep patient NPO for TEE
EchocardiographyTTE and TEE
Consult infectious diseases, cardiology, cardiac surgery, oral
surgery if dentulous
Treatment for congestive heart failure
Oxygen treatment may be indicated.
Hemodialysis may be used if renal failure develops.
Drug Therapy of Choice
Therapy for endocarditis of various causes is outlined in
Tables 5-10.
Precautions
Patients with renal impairmentDosage adjustment should
be made for penicillin G, ampicillin, gentamicin, cefazolin,
and vancomycin.
Rapid infusion of vancomycin (<1 hour) may cause red
man syndrome, an intense redness or rash over upper half
of the body.
This is due to histamine release and not an allergic
reaction.
It disappears when the rate of infusion is decreased.
The combination of vancomycin and gentamicin may cause
increased incidence of renal toxicity.
621
622
Table 5. Therapy for Native Valve Endocarditis Caused by Highly Penicillin-Susceptible (MIC 0.12 g/mL)
Viridans Group Streptococci and Streptococcus bovis
Regimen
Aqueous crystalline
penicillin G sodium or
Ceftriaxone sodium
Dosage & route*

12-18 million U/24 hours IV
continuously or in 6 equally
divided doses
2 g/24 hours IV or IM in 1
dose
Pediatric dose
Penicillin: 200,000
U/kg per 24 hours IV
in 4-6 equally divided
doses
Ceftriaxone: 100 mg/kg
per 24 hours IV or
IM in 1 dose
Duration,
weeks
Strength of
recommendation
4
IA
4
Comments
Preferred for most patients >65 years
or patients with impaired CN VIII
or renal function
Table 5 (continued)
Dosage & route*
Aqueous crystallne
penicillin G
sodium or
Ceftriaxone sodium
plus
Gentamicin sulfate
12-18 million U/24 hours IV

continuously or in 6 equally
divided doses
dose
3 mg/kg per 24 hours IV or
IM in 1 dose
Pediatric dose
Penicillin: 200,000
U/kg per 24 hours IV
doses
per 24 hours IV or IM
in 1 dose
Gentamicin: 3 mg/kg per
24 hours IV or IM in 1
dose or 3 equally divided
doses
Duration,
weeks
Strength of
recommendation
2
IB
2
Comments
2-Week regimen is not intended for
patients with known cardiac or
extracardiac abscess or for those
with creatinine clearance
<20 mL/min, impaired CN VIII
function, or Abiotrophia,
Granulicatella, or Gemella
species infection
Gentamicin dosage should be
adjusted to achieve a peak serum
concentration of 3-4 g/mL &
trough serum concentration
<1 g/mL when 3 divided doses
are used
A nomogram is used for single
daily dosing
III DISEASES
623
Regimen
624
Table 5 (continued)
Regimen
Vancomycin hydrochloride//
Dosage & route*

30 mg/kg per 24 hours IV in
2 equally divided doses,
not to exceed 2 g/24 hours
unless serum levels are
inappropriately low
Pediatric dose: 40 mg/kg
per 24 hours IV in 2-3
equally divided doses
Duration,
weeks
Strength of
recommendation
IB
Comments
Vancomycin therapy is recommended
only for patients unable to tolerate
penicillin or ceftriaxone
Vancomycin dosage should be
adjusted to obtain peak (1 hour after
completion of infusion) serum level
of 30-45 g/mL and trough level of
10-15 g/mL
CN, cranial nerve; MIC, minimum inhibitory concentration.

*Dosages recommended are for patients with normal renal function.
Note that pediatric dose should not exceed that for a normal adult.
Other potentially nephrotoxic drugs (e.g., NSAIDs) should be used with caution in patients receiving gentamicin therapy.
Although data are available for once-daily dosing of aminoglycosides for children, none are available for treatment of infective endocarditis
//Vancomycin dosages should be infused over at least 1 hour to reduce risk of histamine release red-man syndrome.
Table 6. Therapy for Native Valve Endocarditis Caused by Strains of Viridans Group Streptococci and
Streptococcus bovis Relatively Resistant (MIC >0.12 g/mL to 0.5 g/mL) to Penicillin*
Dosage & route
Aqueous crystallne
penicillin G
sodium or
Ceftriaxone sodium
plus
Gentamicin sulfate
24 million U/24 hours IV

continuously or in 4-6
dose
IM in 1 dose
Pediatric dose
Penicillin: 300,000
U/24 hours IV in 4-6
in 1 dose
24 hours in 1 dose or
3 equally divided doses
Duration,
weeks
Strength of
recommendation
4
4
2
IB
Comments
Patients with endocarditis caused
by penicillin-resistant (MIC
>0.5 g/mL) strains should be
treated with a regimen recommended for enterococcal
endocarditis (Table 7)
III DISEASES
625
Regimen
626
Table 6 (continued)
Regimen
Vancomycin hydrochloride
Dosage & route*

2 equally divided doses,
not to exceed 2 g/24 hours
unless serum level is
inappropriately low
per 24 hours in 2 or 3
Duration,
weeks
Strength of
recommendation
IB
Comments
Vancomycin therapy is recommended
only for patients unable to tolerate
penicillin or ceftriaxone
MIC, minimum inhibitory concentration.

See Table 5 for appropriate dosage of gentamicin.
Vancomycin dosages should be infused over at least 1 hour to reduce risk of histamine release red-man syndrome.
Table 7. Therapy for Endocarditis Due to Enterococci

Regimen
Aqueous crystalline penicillin
G sodium
With gentamicin sulfate
Ampicillin sodium

Vancomycin hydrochloride
Duration, weeks
4-6
Comments
4 weeks for patients with symptoms <3

months
6 weeks for patients with symptoms >3
months
4-6
Recommended for patients allergic to

-lactams
4-6
Cephalosporins not acceptable alternatives

for patients allergic to penicillin
627
III DISEASES
Dosage & route

18-30 million U/24 hours
IV continuously or in
1 mg/kg IM or IV every
8 hours
12 g/24 hours IV
continuously or in 6
8 hours
30 mg/kg per 24 hours IV
in 2 equally divided
doses, not to exceed
2 g/24 hours unless
serum levels are
monitored
8 hours
628
Table 8. Therapy for Endocarditis Caused by Staphylococci in Absence of Prosthetic Materials*

Regimen
Dosage & route*
Duration
Strength of
recommendation
Comments
Oxacillin-susceptible strains
Nafcillin sodium or
oxacillin
With optional addition of
gentamicin sulfate
12 g/24 hours IV in 4-6

IM in 2 or 3 equally divided
doses
Pediatric dose
Nafcillin or oxacillin:
200 mg/kg per 24 hours
IV in 4-6 equally
divided doses
Gentamicin: 3 mg/kg
in 3 equally divided
doses
6 weeks
3-5 days
IA
IB
For uncomplicated right-sided IE

(i.e., 2 weeks)
For complicated right-sided IE and
for left-sided IE
Clinical benefit of aminoglycosides
has not been established
Table 8 (continued)
Regimen
Dosage & route*
Duration
Strength of
recommendation
For penicillin-allergic
(non-anaphylactoid
type) patients
Cefazolin
629
4-6 weeks

IM in 2 or 3 equally
divided doses
Pediatric dose
Cefazolin: 100 mg/kg
per 24 hours IV in 3
24 hours IV or IM in
3-5 days
IB
Consider skin testing for oxacillinsusceptible staphylococci and

questionable history of immediatetype hypersensitivity to penicillin
Cephalosporins should be avoided
in patients with anaphylactoidtype hypersensitivity to -lactams;
vancomycin should be used in
these cases
Clinical benefit of aminoglycosides
has not been established
III DISEASES
With optional addition of gentamicin

sulfate
6 g/24 hours IV in 3 equally

divided doses
Comments
630
Table 8 (continued)
Regimen
Dosage & route*
Duration
Strength of
recommendation
Comments
Oxacillin-resistant strains
Vancomycin//

per 24 hours IV in 2 or 3
6 weeks
IB
Adjust vancomycin dosage to achieve

1-hour serum level of 30-45 g/mL
and trough level of 10-15 g/mL
IE, infective endocarditis.

Penicillin G 24 million U/24 hours may be used in place of nafcillin or oxacillin if strain is penicillin-susceptible (minimum inhibitory concentration
0.1 g/mL).
Gentamicin should be administered in close temporal proximity to vancomycin, nafcillin, or oxacillin dosing.
//Vancomycin dosages should be infused over at least 1 hour to reduce risk of histamine release red-man syndrome.
Table 9. Therapy for Prosthetic Valve Endocarditis Caused by Staphylococci (Oxacillin-Susceptible

Strains)*
Dosage & route
Nafcillin or oxacillin
plus
Rifampin
plus
Gentamicin
12 g/24 hours IV in 6 equally

divided doses
900 mg IV or PO in 3 equally
divided doses
IM in 2 or 3 equally divided
doses
Pediatric dose
Nafcillin or oxacillin 200
mg/kg per 24 hours IV
doses
Rifampin: 20 mg/kg per
24 hours PO or IV in
24 hours IV or IM in 3
Duration,
weeks
6
6
2
Strength of
recommendation
IB
Comments
Cefazolin may be substituted for
nafcillin or oxacillin
Penicillin G 24 million U/24 hours
may be used in place of nafcillin
or oxacillin if strain is penicillinsusceptible (MIC 0.1 g/mL) and
does not produce -lactamase
Vancomycin should be used in
patients with immediate-type
hypersensitivity reactions to lactam antibiotics (see Table 5 for
dosing guidelines)
III DISEASES
631
Regimen
632
Table 9 (continued)
Regimen
Vancomycin
plus
Rifampin
plus
Gentamicin
Dosage & route*

30 mg/kg per 24 hours in 2 equally divided
doses
900 mg/24 hours IV or PO in 3 equally
divided doses
3 mg/kg per 24 hours IV or IM in 2 or 3
Pediatric dose
Vancomycin: 40 mg/kg per 24 hours IV
in 2 or 3 equally divided doses
Rifampin: 20 mg/kg per 24 hours IV or
PO in 3 equally divided doses (up to the
adult dose)
Gentamicin: 3 mg/kg per 24 hours IV or
IM in 3 equally divided doses
Duration,
weeks
Strength of
recommendation
IB
6
2
MIC, minimum inhibitory concentration.

Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing.
Comments
Adjust vancomycin to achieve
1-hour serum level of
30-45 g/mL and trough
level of 10-15 g/mL
Table 10. Therapy for Both Native Valve and Prosthetic Valve Endocarditis Caused by HACEK
Microorganisms
Regimen
Ceftriaxone sodium
or
Dosage & route
Duration,
Strength of
weeks
recommendation
2 g/24 hours IV or IM in
1 dose*
IB
IIaB
IIbC
Cefotaxime or another 3rd- or

4th-generation cephalosporin may
be substituted
Fluoroquinolone therapy is recommended only for patients unable to

tolerate cephalosporin & ampicillin
Levofloxacin, gatifloxacin, or
moxifloxacin may be substituted
Fluoroquinolones are generally not
recommended for patients <18 years
633
III DISEASES
Ampicillin-sulbactam 12 g/24 hours IV in 4 equally

or
divided doses
Ciprofloxacin
1,500 mg/24 hours PO or 800
mg/24 hours IV in 2 equally
divided doses
Pediatric dose
Ceftriaxone: 100 mg/kg per
24 hours IV or IM once
daily
Comments
634
Table 10 (continued)
Regimen
Dosage & route*

Ampicillin-sulbactam: 300
mg/kg per 24 hours IV
in 4 or 6 equally divided
doses
Ciprofloxacin: 20-30 mg/kg
per 24 hours IV or PO in
Duration,
weeks
Strength of
recommendation
Comments
Prosthetic valve: Patients with
endocarditis involving a prosthetic
cardiac valve or other prosthetic
cardiac material should be treated
for 6 weeks
HACEK (see Table 1).

*Patients should be informed that IM injection of ceftriaxone is painful.
Dosage recommended for patients with normal renal function.
Fluoroquinolones are highly active in vitro against HACEK microorganisms. Published data on use of fluoroquinolone therapy for endocarditis caused
by HACEK are minimal.
Note that the pediatric dose should not exceed that for a normal adult.
III DISEASES
Rifampin may increase the requirement for warfarin oral

anticoagulant and oral hypoglycemic agents.
Gentamicin blood levels should be determined if treatment
is >5 days and for patients with renal dysfunction.
Peak gentamicin level should be about 3 g/mL and trough
<1 g/mL.
Vancomycin blood levels should be determined in patients
with renal dysfunction.
Desired peak level is 30-45 g/mL and trough <10 g/mL.
BUN and serum creatinine should be measured twice weekly
while patient is receiving gentamicin.
Consider audiometry baseline and follow-up during longterm aminoglycoside therapy.
Gentamicin should be used with caution or avoided if possible
in pregnant women.
Alternative Drugs for Patients Allergic to Penicillin

Endocarditis due to penicillin-susceptible viridans streptococci and Streptococcus bovis
Ceftriaxone 2 g IM or IV every 24 hours (not for patients
with immediate-type hypersensitivity to penicillin) or
Vancomycin 15 mg/kg (usual dose, 1 g) IV infused over
1 hour every 12 hours for 4 weeks (6 weeks for prosthetic
valve endocarditis)
Endocarditis due to enterococci
Desensitization to penicillin should be considered.
Vancomycin 15 mg/kg (usual dose, 1 g) IV infused over
1 hour every 12 hours plus gentamicin (3 mg/kg/day in
divided doses q 8-12 hours, depending on renal function
and results of peak and trough measures) for 4-6 weeks (6
weeks for prosthetic valve endocarditis)
Surgical Measures
Cardiac surgery to replace infected valve may be performed
before the course of antibiotic treatment is completed when
one of the following occurs:
Evidence of congestive heart failure due to valve incompetence
635
Multiple major systemic emboli

Infection caused by resistant organisms, e.g., Aspergillus,
Candida, other fungi, Pseudomonas aeruginosa
Dehiscence of infected prosthetic valve
Relapse of prosthetic valve endocarditis
Persistent bacteremia despite antibiotic treatment
RISK FACTORS
High-risk categoryantimicrobial prophylaxis recommended
for invasive procedures (dental work, genitourinary tract,
some endoscopic procedures)
Prosthetic cardiac valves, including bioprosthetic and
homograft valves
Previous bacterial endocarditis, even in the absence of
heart disease
Complex cyanotic congenital heart disease (e.g., singleventricle states, transposition of great arteries, tetralogy of
Fallot)
Surgically constructed systemic pulmonary shunts or
conduits
Moderate-risk categoryprophylaxis recommended
Most other congenital cardiac malformations (other than
those listed above and below)
Acquired valvular dysfunction (e.g., rheumatic heart disease)
Hypertrophic cardiomyopathy
Mitral valve prolapse with valvular regurgitation and/or
thickened leaflets
Negligible-risk category (not greater than that of the general
population)prophylaxis not recommended
Isolated secundum atrial septal defect
Surgical repair of atrial septal defect, ventricular septal
defect, or patent ductus arteriosus (without residual beyond
6 months)
Previous coronary artery bypass graft surgery
Mitral valve prolapse without valvular regurgitation
Physiologic, functional, or innocent heart murmurs
Previous Kawasaki disease without valvular dysfunction
Previous rheumatic fever without valvular dysfunction
Cardiac pacemakers (intravascular and epicardial) and
implanted defibrillators
636
III DISEASES
PREVENTION AND PROPHYLAXIS
Who should receive antibiotic prophylaxis?
All patients with high- and moderate-risk factors undergoing
Dental extractions
Periodontal procedures, including surgery, scaling and
root planing, probing, and recall maintenance
Dental implant placement and reimplantation of avulsed
teeth
Endodontic (root canal) instrumentation or surgery only
beyond the apex
Subgingival placement of antibiotic fibers or strips
Initial placement of orthodontic bands but not brackets
Intraligamentary local anesthetic injections
Prophylactic cleaning of teeth or implants when bleeding is anticipated
Respiratory tract procedures
Tonsillectomy and/or adenoidectomy
Surgical operations involving respiratory mucosa
Bronchoscopy with rigid bronchoscope
Genitourinary tract procedures
Prostatic surgery
Cystoscopy
Urethral dilation
All patients with high-risk factors (optional for those with
moderate-risk factors) undergoing gastrointestinal tract
procedures
Sclerotherapy for esophageal varices
Esophageal stricture dilation
Endoscopic retrograde cholangiography for biliary
obstruction
Biliary tract surgery
Surgical operations involving intestinal mucosa
Endocarditis prophylaxis is not recommended for
Patients with negligible risks
The following dental procedures:
Restorative dentistry (operative and prosthodontic) with
or without retraction cord
Local anesthetic injections (nonintraligamentary)
637
Intracanal endodontic treatment; postplacement and

build-up
Placement of rubber dams
Postoperative suture removal
Placement of removable prosthodontic or orthodontic
appliances
Taking of oral impressions
Fluoride treatments
Taking of oral X-rays
Orthodontic appliance adjustment
Shedding of primary teeth
The following respiratory tract procedures:
Endotracheal intubation
Bronchoscopy with flexible bronchoscope, with or without biopsy
Myringotomy tube insertion
The following gastrointestinal tract procedures:
TEE
Endoscopy with or without gastrointestinal biopsy
The following genitourinary tract procedures:
Vaginal hysterectomy
Vaginal delivery
Cesarean section
In uninfected tissue
Urethral catheterization
Uterine dilatation and curettage
Therapeutic abortion
Sterilization procedures
Insertion or removal of intrauterine devices
The following other procedures:
Cardiac catheterization, including balloon angioplasty
Implanted cardiac pacemakers, implanted defibrillators, and coronary stents
Incision or biopsy of surgically scrubbed skin
Circumcision
Antibiotic prophylaxis
Antibiotics administered more than 4 hours after the procedure probably have no prophylactic effect.
Generally, prophylaxis should be administered PO 1 hour
and IM/IV within 0.5 hour before the procedure in adults
and children (Tables 11 and 12)
638
III DISEASES
Prophylaxis should not be extended more than 24 hours

postoperatively.
COURSE AND PROGNOSIS

In staphylococcal endocarditis, fever may persist up to 5
days and positive blood cultures may persist up to 5 days
after appropriate treatment is started
In streptococcal endocarditis, clinical response should occur
within 48 hours after starting antibiotic treatment and blood
cultures should be negative soon after antibiotic treatment is
started.
Prognosis depends largely on the possible complications.
Prognosis is worse for elderly persons.
Table 11. Prophylactic Regimens for Dental, Oral,

Respiratory Tract, or Esophageal Procedures
Situation
Agent
Standard
Amoxicillin
Unable to take PO
Ampicillin
Allergic to penicillin
Clindamycin or
& unable to take PO
Regimen
A:
C:
A:
C:
A:
C:
2.0 g PO
50 mg/kg PO
2.0 g IM/IV
50 mg IM/IV
600 mg PO
20 mg/kg PO
Cephalexin or
Cefadroxil or
A: 2.0 g PO
C: 50 mg/kg PO
Azithromycin or
Clarithromycin
Clindamycin or
A:
C:
A:
C:
A:
C:
Cefazolin
500 mg PO
15 mg/kg PO
600 mg IV
20 mg/kg IV
1.0 g IM/IV
25 mg/kg IM/IV
A, adult; C, child.
639
Table 12. Prophylactic Regimens for Genitourinary or

Gastrointestinal Procedures
Situation
Agent
High-risk patients
Ampicillin plus
gentamicin
High-risk patients
allergic to
ampicillin
Moderate-risk
patients
640
Regimen
Ampicillin
Adults: 2 g
Children: 50 mg/kg
Gentamicinadults
& children: 1.5 mg/kg
30 Minutes before
procedure & ampicillin
1 g 6 hours later
Vancomycin plus Vancomycin
gentamicin
Adults: 1 g
Children: 20 mg/kg
Gentamicinfor adults
& children: 1.5 mg/kg
Complete infusion 30
minutes before procedure
Same regimens as in Table 11
III DISEASES
INFLAMMATORY BOWEL DISEASE
Conor G. Loftus, M.D.
Edward V. Loftus, Jr., M.D.
DEFINITION
Inflammatory bowel disease (IBD) encompasses at least two
forms of idiopathic intestinal inflammation (ulcerative colitis
and Crohn disease).
Absence of a specific underlying etiologic agent sets IBD
apart as a cause of intestinal inflammation.
CLASSIFICATION
Classification is based on typical clinical, pathologic,
endoscopic, radiologic, and lab features.
The broad classification of IBD
Ulcerative colitisconfined to colon
Crohn disease (regional enteritis, regional ileitis, Crohn
ileitis, and granulomatous colitis)may involve any
portion of the gastrointestinal tract
Indeterminate colitiscases in which it is impossible to
distinguish with confidence between ulcerative colitis and
Crohn disease affecting the colon by using any conventional diagnostic criteria
ETIOLOGY
Exact cause of ulcerative colitis and Crohn disease is
unknown.
They may result from interaction between genetically determined host susceptibility and acquired environmental
influences
Genetic Factors
Frequency of disease in first-degree relatives of patients with
IBD is 5%-10%.
Special abbreviation used in this chapter: IBD, inflammatory bowel disease.

641
High concordance of disease in monozygotic twin pairs

(Crohn disease > ulcerative colitis)
Identical twin of a patient does not uniformly develop IBD,
so nongenetic factors are also involved.
Infection
Atypical mycobacteria, cell-wall deficient bacteria, and
previous exposure to measles (rubeola) are implicated as
potential causes, but this is controversial.
Bacterial or viral gastroenteritis may serve as an environmental trigger for IBD.
Smoking
Ulcerative colitis
More common in nonsmokers
Risk is particularly high for ex-smokers, especially within first 2 years after cessation.
Crohn disease
Smoking increases the risk.
Psychosocial Factors
Environmental stress may have a role in IBD flares.
Medications
Ulcerative colitis and Crohn disease are frequently exacerbated by NSAIDs.
Role of oral contraceptive pills in exacerbations of IBD is not
clear.
EPIDEMIOLOGY
Epidemiologic features of IBD are listed in Table 1.
Ulcerative Colitis
Symptoms
Classicbloody diarrhea
Commonfatigue, fever, abdominal pain, rectal pain,
tenesmus, rectal urgency
Signs
Mild diseasemild abdominal tenderness
Severe diseasehypotensive, tachycardic, febrile, dry
642
III DISEASES
Table 1. Epidemiologic Features of Inflammatory Bowel
Disease
Incidence/100,000
Prevalence/100,000
Race
Sex
Age at onset, years
Ethnic
Smoking
Relapse association
CD 1-10
UC 2-18
CD 20-150
UC 40-250
White>black>Hispanic>Asian
UC M>F
CD peak 15-30
UC peak 20-40
Jewish>non-Jewish
Predisposes CD
Protective UC
NSAIDs
CD, Crohn disease; UC, ulcerative colitis.
mucosae, pallor, marked abdominal tenderness (often

rebound), guarding, hypertympanism (consider toxic
megacolon), decreased bowel sounds
Crohn Disease
Symptoms
Classicdiarrhea, abdominal pain, weight loss
Commonfatigue, weight loss, diarrhea, steatorrhea,
cramping right lower abdominal pain, bloating, nausea,
vomiting, epigastric pain
Signs
Pale, ill-appearing, cachectic, muscle-wasting, clubbing,
abdominal distension, right lower quadrant tenderness or
mass, perianal fistulous opening or abscess
Compared with ulcerative colitis, Crohn disease has a
more varied presentation because of the
Diversity of anatomic involvement
Transmural nature of the inflammatory process
Differential Diagnosis for Fulminant Colitis and Toxic

Megacolon
The differential diagnosis is listed in Table 2.
643
Table 2. Differential Diagnosis for Fulminant Colitis and

Toxic Megacolon
Ulcerative colitis
Crohn colitis
Infectious colitis
Shigella
Salmonella
Aeromonas hydrophila
Campylobacter
E. coli O157:H7
Amoeba
Cytomegalovirus (immunosuppressed)
Medication-related
Gold
Methotrexate
NSAIDs
Estrogen
Ischemic colitis
Kaposi sarcoma
Neutropenic colitis
Complications
Emergent complications in IBD are classified as shown in
Figure 1.
Intestinal Complications
The incidence of fulminant colitis is approximately 5%10%; incidence of toxic dilatation in ulcerative colitis in the
modern era is lower.
Perforation occurs in up to one-third of patients with toxic
megacolon.
Perforation may also occur in fulminant colitis without
colonic dilatation.
Free perforation with generalized peritonitis is rare in
Crohn disease; microperforation with localized peritonitis is more common, especially right lower quadrant.
Bloody diarrhea occurs in 95% of patients with ulcerative
colitis.
Intra-abdominal abscesses complicate Crohn disease in 12%25% of patients and are more common in ileocolitis than in
isolated ileitis or colitis.
644
Complications
Intestinal
Ulcerative colitis
Crohn disease
Bowel obstruction
Intra-abdominal abscess
Fistula
Perforation
Hemorrhage
Toxic megacolon
Pancreatitis
Gallstone disease
Thromboembolic disease
Arthritis
Ocular manifestations
Urologic manifestations
645
Fig. 1. Emergent complications of inflammatory bowel disease.
III DISEASES
Toxic megacolon
Perforation
Hemorrhage
Extraintestinal
Extraintestinal Complications
Pancreatitis
Duodenal Crohn disease may obstruct the pancreatic duct
or render the sphincter of Oddi incompetent.
In IBD, bile is lithogenic, predisposing to biliary sludge or
stones and secondary pancreatitis.
IBD medicationsazathioprine, 6-mercaptopurine,
sulfasalazine, mesalamine, olsalazine, and metronidazolehave been implicated in development of
pancreatitis.
Gallstone disease
Extensive ileal disease or resection decreases bile acid
pool, rendering bile lithogenic.
Thromboembolic disease
Hypercoagulable state in IBD is caused by increased factors V and VIII, thrombocytosis, abnormal platelet activity,
and decreased antithrombin III.
Patients may present acutely with deep venous thrombosis
or pulmonary embolism.
Dilemmawhen patients have active colitis with
pronounced bleeding. In this setting, anticoagulation with
heparin is well tolerated, but colectomy may be required
for bleeding or recurrent thromboembolism.
Patients with IBD rarely present with cerebrovascular
accidents due to arterial thrombosis.
Seronegative arthritis
IBD may be associated with both peripheral and axial
arthritis.
Patient may present with acute arthritis; aspirate synovial
fluid to rule out septic arthritis.
Treatment is directed at the intestinal disease; use NSAIDs
with caution because they may exacerbate IBD.
Axial arthropathy (sacroiliitis and spondylitis) is independent of intestinal activity.
Peripheral arthritis follows activity of intestinal disease,
axial arthropathy does not.
Dermatologic disease
Erythema nodosum
Pyoderma gangrenosum
Aphthous ulcers
Ocular manifestations
646
III DISEASES
Ocular emergencies include episcleritis and anterior
uveitis.
Episcleritis parallels intestinal disease activity; anterior
uveitis does not.
Consult ophthalmology.
Urologic manifestations
Urolithiasis
Uric acid stones are common because of chronic dehydration, the metabolic acidosis induced by diarrhea,
and hypercatabolic state associated with IBD.
Crohn patients with extensive disease or resection who
have malabsorption develop calcium oxalate stones.
Urosepsis
This may result from chronic enterovesical fistula, and
patient may complain of pneumaturia or fecaluria.
Pyelonephritis can occur from obstructive uropathy.
Crohn disease can fistulize posteriorly, encasing the
ureter and causing obstruction. This is more likely to
occur on the right side, with consequent hydroureter,
hydronephrosis, and complicating urosepsis.
Diagnosis of IBD relies on
Clinical and lab data
Imaging (barium studies or CT)
Endoscopy (esophagogastroduodenoscopy, colonoscopy,
flexible sigmoidoscopy, capsule endoscopy)
Pathology
Stepwise approach for diagnosing ulcerative colitis and
Crohn disease is provided in Table 3.
Physical Exam
Ill-appearing, febrile, orthostatic, tachycardic, abdominal
guarding, absent bowel sounds, tympanic percussion note
Investigations
Stool samples for ova, parasites, bacterial culture, and
Clostridium difficile toxin
647
Table 3. Stepwise Approach to Diagnosis of Ulcerative

Colitis and Crohn Disease According to Type of
Investigation
Investigation
Ulcerative colitis
Clinical
Bloody diarrhea
Lab
CBC
Electrolytes
Inflammatory
markers
Albumin
Other
Radiologic
Distribution
Ulceration
Fissures
Strictures or
fistulas
Ileal involvement
Endoscopic
Friability
Aphthous &
linear ulcers
Cobblestone
appearance
Pseudopolyps
Rectal involvement
Distribution
648
Crohn disease
Diarrhea
Weight loss
Abdominal pain
Right lower quadrant
mass
Perianal disease
Anemia (iron,
Anemia (iron, TIBC,
TIBC), leukocytovitamin B12, folate),
sis, thrombocytosis leukocytosis, thrombocytosis
Hypokalemia
Hypokalemia
ESR, CRP
ESR, CRP
Low in severe
disease
Elevated p-ANCA
Low in severe disease
Continuous,
symmetric
Fine, superficial
Discontinuous,
asymmetric
Deep, submucosal
extension
Often
Common
Never
Rare
Elevated ASCA
Dilated, backwash
iliitis (uncommon)
Narrowed, nodular,
erosions, ulcers
(common)
Characteristic
Rare
Occasional
Common
Never
Common
Common
95%
Occasional
50% of cases
Continuous, distal
Discontinuous, skip
lesions
III DISEASES
Table 3 (continued
Investigation
Pathologic
Focal granulomas
Transmural
inflammation
Deep fissures,
fistulas
Macroscopic
thickening
Narrowing of
bowel lumen
Ulcerative colitis
Crohn disease
Never
Common
Rare
Common
Never
Common
Rare
Common
Rare
Common
ASCA, anti-Saccharomyces cerevisiae antibody; CRP, C-reactive protein; pANCA, perinuclear antineutrophil cytoplasmic antibody; TIBC, total ironbinding capacity.
Abdominal supine and upright X-raysloss of colonic haustra, thumbprinting indicating bowel-wall edema, colonic
dilatation (especially transverse colon)
Severity
Criteria for assessing severity of ulcerative colitis are listed
in Table 4.
MANAGEMENT
General
NPO
Fluid and electrolyte replacement, transfusion of blood products as required
Nasogastric tube if toxic megacolon
Corticosteroidsmethylprednisolone, 20-40 mg IV every
12 hours
Antibioticscefotaxime, 1 g IV every 8 hours + metronidazole, 500 mg IV every 8 hours if patient is toxic, febrile,
has leukocytosis, etc.
Serial abdominal X-rays, especially if toxic megacolon
649
Table 4. Criteria for Assessing Severity of Ulcerative

Colitis
Variable
Bowel movements
Mild
<4/day
Minimal blood
Fever
None
Pulse, beats/minute
<90
Hemoglobin,
>12
g/L
ESR, mm/1 hour
<10
Albumin, g/dL
>3.5
Moderate
Severe
4-6/day
Bloody
90-100
9-12
>6/day
Bloody
>99.5F
>100
<9
10-30
3-3.5
>30
<3
Data from Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on
a therapeutic trial. Br Med J. 1955;2:1041-8.
Surgical consultation
Colectomy if unresolving with medical therapy or clinical
deterioration
Medical Management if IBD

5-Aminosalicylates
Oral
Sulfasalazine (Azulfidine)4-6 g daily in 4 divided doses
Sulfa-free agents
Mesalamine (Asacol, Pentasa)2-4 g daily in divided
doses
Balsalazide (Colazal)6.75 g daily in divided doses
Olsalazine (Dipentum)1.5-3 g daily in divided doses
Rectal
Mesalamine suppository (Canasa)500 mg twice daily
(proctitis)
Mesalamine enema (Rowasa)4 g daily (for distal colitis)
5-Aminosalicylates for mild or moderate disease and maintenance therapy
Sulfa-free agents
Efficacy in ulcerative colitis comparable with sulfasalazine
Fewer undesirable effects
Corticosteroids
Classic
Prednisone40-60 mg PO daily, taper by 5 mg/week over
2-3 months
650
III DISEASES
Methylprednisolone (Solu-Medrol)IV 40-60 mg daily
(for severe IBD flares)
Hydrocortisone enema (Cortenema)100 mg twice daily
(for acute management of distal colitis)
Novel
Budesonide (Entocort EC)
6-9 mg PO daily (controlled ileal release formulation)
High potency and low bioavailability for minimizing
adverse systemic effects
Immunomodulators
Azathioprine/6-mercaptopurine
For patients resistant to or dependent on corticosteroids
Azathioprinea prodrug yielding 6-mercaptopurine
Azathioprine, 2.0-2.5 mg/kg body weight, and 6-mercaptopurine, 1-5 mg/kg body weight
Monitor for myelosuppression, especially leukopenia.
Methotrexate
IM or SQ for Crohn disease, not for ulcerative colitis
Induction dose25 mg/week
Maintenance dose15 mg/week
Time to onset of response may be more rapid than for azathioprine/6-mercaptopurine.
Cyclosporine
May be used for IBD flares refractory to other treatments
Administered as a continuous infusion2-4 mg/kg daily
Mean response time of 7 days
Monitor for hypertension, renal insufficiency
Antibiotics
Metronidazole (Flagyl)
Beneficial for
Mild to moderate Crohn disease
Perianal and fistulous Crohn disease
Postoperative prophylaxis
Pouchitis following ileoanal pouch surgery
Ciprofloxacin (Cipro)
In Crohn disease, it has been used as a single agent or in
651
combination with metronidazole for active disease and

fistulas.
Biologic Response Modifiers
Infliximab (Remicade)
Chimeric monoclonal antibody to tumor necrosis factor
Approved for treating refractory or fistulizing Crohn
disease
For moderate to severe Crohn disease, 5 mg/kg IV infusion
on weeks 0, 2, and 6, followed by every 8 weeks
For fistulizing Crohn disease, 5 mg/kg on weeks 0, 2, and 6,
followed by every 8 weeks
Acute infusion reactions are rare.
Delayed hypersensitivity reactions after 3-10 days because
human antichimeric antibodies develop
Perform PPD (tuberculin test) and chest X-ray before initiating therapy (reactivation of latent TB can occur).
CANCER SURVEILLANCE
After 10 years of extensive ulcerative colitis, cancer risk is
about 0.5%-1%/year.
Patients with left-sided colitis reach similar levels of cumulative risk after 3-4 decades.
After 8-10 years of colitis, surveillance colonoscopy with
multiple biopsies should be performed every 1 to 2 years.
Definite dysplasia of any grade, confirmed by expert pathologist, is indication for colectomy.
652
III DISEASES
MYASTHENIA GRAVIS AND DISORDERS
OF THE NEUROMUSCULAR JUNCTION
Kathleen M. McEvoy, M.D.
DEFINITION
Myasthenia gravis is an acquired autoimmune disorder in
which pathogenic autoantibodies destroy acetylcholine receptors (AChRs) at the neuromuscular junction.
It is a pure motor syndrome characterized by weakness and
fatigue of extraocular, pharyngeal, facial, cervical, proximal
limb, and respiratory musculature.
Onset may be sudden and severe, but more typically is mild
and intermittent over many years.
CLASSIFICATION
Clinical classification is based on distribution and severity of
symptoms, as follows:
Type 1 (20% of cases)confined to extraocular muscles
Type 2A (30%)mild generalized weakness (cranial,
trunk, limb)
Type 2B (20%)moderately severe generalized weakness
Type 3 (11%)acute fulminating (early respiratory
involvement)
Type 4 (9%)late severe
ETIOLOGY
Humoral and cellular immune-mediated destruction of postsynaptic AChRs at neuromuscular junction
Weakness results from decreased number of functional
AChRs at neuromuscular junction secondary to destruction
by pathogenic autoantibodies.
Thymic abnormality is believed to be involved in the
Special abbreviation used in this chapter: AChR, acetylcholine receptor.

653
pathogenesis of autoimmune myasthenia gravis, perhaps

by triggering recognition of self AChR as nonself.
Neonatal myasthenia gravis10%-15% of infants born to
myasthenic mothers develop neonatal myasthenia gravis
from transplacental transfer of AChR antibodies.
It typically presents as feeble cry, feeding and respiratory difficulty, general or facial weakness, and ptosis, which
may resolve completely in several weeks.
EPIDEMIOLOGY
Myasthenia gravisthe most common disorder of the neuromuscular junction
Prevalence, 3/100,000 (13-64 per million)
Incidence, 2-5/million people annually
Female:male ratio, 3:2
May present at any age
Incidence in women peaks in third decade.
Incidence in men peaks in fifth to seventh decades.
Familial predisposition (5% of cases) with an increased frequency of HLA-B8 and DR3
HLA studies show increased association with other autoimmune disorders (Hashimoto thyroiditis, rheumatoid arthritis, and pernicious anemia).
Thymomain 10%-15% of patients, especially if older
than 40
Thymic hyperplasiain 85% of patients younger than 40
Classic Presentation
Clinical hallmark is fluctuating muscle weakness of ocular,
cranial, and bulbar muscles producing diplopia, ptosis, and
dysphagia.
Common Presentation
May include generalized weakness, fatigue with chewing,
dysarthria, dysphonia, neck weakness, proximal limb weakness, and respiratory weakness
Exacerbating Factors
May include emotional stress, exercise and heat, illness
and infection, fever, hormonal imbalance, drug-induced
654
III DISEASES
(corticosteroids, aminoglycosides, tetracyclines, quinidine,
procainamide, -blockers, lidocaine, narcotics, and psychotropics)
Complications
Crisis (Myasthenic vs. Cholinergic)
In myasthenia gravis, severe muscle weakness and respiratory failure can result from not enough functional acetylcholine receptors (myasthenic crisis) or too much acetylcholine (cholinergic crisis).
Cholinergic crisis
Typically caused by overdose of anticholinergic medications
Suspect cholinergic crisis when other signs of cholinergic overactivity (excessive secretions, diarrhea, bradycardia) are present.
Treat with atropine, 0.4 mg IV.
Myasthenic crisis
Most likely cause is infection with undertreatment of
myasthenia gravis.
A potential respiratory emergency!
Myasthenic vs. cholinergic
Distinguish the two types of crisis by a test dose of
edrophonium (Tensilon)2 mg IV of edrophonium
usually increases muscle weakness if the patient is on
the verge of a cholinergic crisis. If no change in muscle
activity occurs after the initial dose, an additional 8 mg
of edrophonium, for a total of 10 mg, may be administered.
Patients experiencing a myasthenic crisis typically
improve with edrophonium.
Corticosteroids
Acute complicationsAdministration of corticosteroids
can cause a transient exacerbation of weakness within the
first 5-7 days after administration (lasting 1-20 days).
Chronic complicationsLong-term corticosteroid use can
cause a myriad of adverse effects.
655
Diagnosis is based on history, physical exam, anticholinesterase testing, and lab studies.
Physical Exam
Examine using provocative maneuvers to induce weakness
by asking the patient to do the following:
Look up without closing the eyes for 1 minute
Count loudly from 1 to 100
Hold the arms elevated for 3 minutes
Perform repeated deep knee bends (normal, 10-20)
Anticholinesterase Tests
Edrophonium (Tensilon) testinitial dose is 2 mg IV. If no
response or side effects, give 8 mg IV. A positive test shows
improvement of strength within 30 seconds after administration. (Use atropine 0.4 mg IV as antidote for severe
bradycardia.)
Atropine-neostigmine test0.5 g atropine IM (control), then
1.5-2.0 mg neostigmine IM. A positive test shows improvement within 10 minutes after administration.
Lab Studies
Electrophysiology Testing
Repetitive motor stimulation at 2-3 HzA decrease >15%
in amplitude of the compound muscle action potential is
highly suggestive of myasthenia gravis.
Single fiber EMGThis assesses the temporal variability
between two muscle fibers within the same motor unit (jitter)
commonly seen in myasthenia gravis. It is highly sensitive
but less specific than repetitive stimulation and technically
difficult to perform.
Anti-AChR Antibodies
Diagnostic test of choice
Detection of anti-AChR antibodies is positive in
Nearly 100% of patients with moderately severe disease
80% with mild generalized disease
50% with ocular myasthenia gravis
Only 25% of those in remission
Highly sensitive and specific assay
656
III DISEASES
Other Studies
MRI, CT of mediastinum to detect thymoma
MANAGEMENT OF ACUTE AND CHRONIC CONDITION
Acute Crisis
Weakness sufficient to cause respiratory failure
General Measures
Temporarily stop anticholinesterase drugs to rule out cholinergic crisis.
Most common cause of myasthenic crisis is infection: look
for it!
Myasthenic patient with fever and infection should be treated
the same way as any immunocompromised patient.
Manage respiratory assistance in ICU.
Supportive Management
May include intubation, tracheostomy, artificial ventilation,
respiratory therapy, antibiotics, and nasogastric tube and/or
gastrostomy.
Medical Therapy
Pyridostigmine bromide (Mestinon)first-line treatment
For daytime use, 60-mg tablets and for nighttime use,
180-mg sustained release tablets. Elixir is available.
Titrate dosage to symptoms (average dose, 600 mg/day).
Initial dose, 60 mg every 3-4 hours
Effects are apparent within 15-30 minutes and peak 1-2
hours after administration.
Increase dose 30 mg every several days as tolerated.
Watch for muscarinic side effects (diarrhea, abdominal
cramps, salivation, nausea).
Neostigmine methylsulfate (Prostigmin)
Concentrations of 0.25, 0.5, and 1 mg/mL
Titrate dosage to clinical need (starting dosages, 0.5 mg SQ
or IM every 3 hours or continuous IV infusion at 1/45 of
the total daily dose of pyridostigmine over 24 hours if
unable to take oral medications).
657
Plasmapheresis
Indicationsevere generalized or fulminating myasthenia
gravis refractory to other forms of treatment
Three to four daily exchanges of 2 L of plasma result in
objective improvement and decreased AChR antibody
titer.
Prednisone
Initial dose, 60-80 mg daily
Long-Term Therapy
General Management
Encourage patients to listen to their bodies!
Advise them to avoid intense exercise and sick contacts.
Update immunizations with Pneumovax and influenza
vaccines.
Medical Therapy
Prednisone
Alternate-day prednisone treatment induces remission or
markedly improves the disease in >50% of patients (average
time, 5 months).
After improvement reaches a plateau, gradually lower the
dose over several months to establish minimal maintenance
dose (typically 35 mg every other day).
Azathioprine
150-200 mg daily (2-3 mg/kg daily) induces remissions in
>50% of patients in 3-12 months.
Survey for side effects (pancytopenia, leukopenia, serious
infection, and hepatocellular injury).
Azathioprine as adjunct to alternate-day prednisone reduces
maintenance dose of prednisone required, lessening side
effects.
Mycophenolate Mofetil
1,000 mg twice daily may control symptoms more quickly
than azathioprine.
Requires similar monitoring for side effects as azathioprine
Cyclophosphamide
150-200 mg daily
658
III DISEASES
Immune Globulin
IV immunoglobulin at 400 mg/kg for 5 consecutive days
may improve severe disease within 2-3 weeks.
Cyclosporine
Is equally effective as azathioprine, with more rapid onset of
benefit
Usual dose, 4-5 mg/kg daily, given in two divided doses
Relatively high risk of renal dysfunction and hypertension
Thymectomy
Increases remission rate and improves clinical course of
disease
Although controlled clinical studies of thymectomy according to age, sex, severity, and duration of disease have never
been performed, there is general agreement that the best
response occurs in young women with hyperplastic thymus
glands and high antibody titer.
Generally recommended routinely to patients with myasthenia
who are younger than 40 years; rarely recommended if older
than 60 years
659
III DISEASES
NEUTROPENIA

Common infections can be life threatening in hours in neutropenic patients.
Neutropenia may be the first manifestation of acute leukemia
that requires prompt evaluation and chemotherapeutic treatment.
ADDRESSING THE RISK
It is critical to instruct patients who are or may become neutropenic (i.e., after chemotherapy) to call immediately when
fever or symptoms of infection develop.
Instruct them not to take antipyretics and wait until
morning.
Neutropenic fever should always be treated as an emergency.
Fever (>38.0C) or symptoms of infection (cough, sore throat,
rash, diarrhea) require immediate evaluation in neutropenic
patients.
Neutropenia is defined by an absolute neutrophil count <1.5
109/L.
Absolute neutrophil count = total WBCs % neutrophils
Severity of the neutropenia is clinically important, with risk
of infection increasing substantially with neutrophil counts
<0.5 109/L.
Most patients with neutropenia have a known malignancy and
experience neutropenia because of myelosuppressive effects
of chemotherapy.
Special abbreviations used in this chapter: HSV, herpes simplex virus; MRSA,
methicillin-resistant Staphylococcus aureus.
661
A short differential of the causes of neutropenia is listed in

Table 1.

Patients with de novo neutropenia (i.e., no recent
chemotherapy)
Evaluate blood smear for blasts.
Stop offending medications (see list in Table 1).
Check vitamin B12, folate, HIV, antinuclear antibody.
Consider bone marrow biopsy.
Perform peripheral blood T-cell gene rearrangement study,
and consider flow cytometry to identify a large granular
lymphocyte disorder.
Consult hematology.
Differentiating the causes of neutropenic fever
General principleNeutropenic patients have limited
ability to mount an inflammatory response. Typical signs
and symptoms of infection are often absent.
History
Date of last chemotherapy? (Review expected timing
and duration of neutropenia for a given chemotherapeutic protocol, often 7-14 days after treatment.)
Does patient have indwelling catheter? (Raises question of line infection)
Does patient have symptoms of cough, sore throat, rash,
diarrhea, cold sores, abdominal pain?
Does patient have history of cold sores? (Raises question of herpes simplex virus [HSV] infection)
Table 1. Causes of Neutropenia

Chemotherapy
Hematologic disordersacute leukemia, lymphoma, myelodysplastic syndrome, aplastic anemia, myelofibrosis, congenital disorders
InfectiousEpstein-Barr virus, HIV, cytomegalovirus, TB, malaria
Medicationticlopidine, propylthiouracil, olanzapine, clozapine, gold,
penicillin, sulfa, ganciclovir, NSAIDs, carbamazepine, phenytoin,
valproic acid, furosemide, thiazides, tricyclic antidepressants
Nutritionalvitamin B12 deficiency, folate
Othersystemic lupus erythematosus, Felty syndrome, myelophthisis, cyclic neutropenia
662
III DISEASES
Physical exam
Examine oropharynx, lungs, abdomen, skin (search for
source of infection).
Inspect site of indwelling catheters for erythema or
drainage (search for evidence of line infection).
Evaluate dentition (search for oral abscess and likelihood
of anaerobic infection).
Inspect perineal region for abscess, and palpate perianal area. Standard practice is to avoid the rectal exam,
but evidence supporting this practice is lacking.
TEST ORDERING
CBC with differential and absolute neutrophil count
Pan culture (blood, urine, sputum). Draw blood specimens
from each lumen of indwelling lines for culture studies.
Include fungal cultures of blood.
Urinalysis (patients with neutropenia often do not have pyuria
even if they have urinary tract infection)
BUN, creatinine
Chest X-ray (may fail to show consolidation when absolute
neutrophil count is low)
Directed imaging by symptoms (sinus CT if sinus pain or
drainage; abdominal CT if abdominal pain, evaluate for
typhlitis)
If new murmur and bacteremic, consider echocardiography
(possible secondary seeding of heart valves).
MANAGEMENT OF NEUTROPENIC FEVER

Admit patient.
Empiric treatment with broad-spectrum antibiotics for all
patients
Imipenem-cilastatin, cefepime, ceftazidime, ticarcillin are
all acceptable (select on basis of the formulary and local
sensitivities).
Add vancomycin empirically if evidence of line infection
on physical exam or if preliminary culture grows grampositive cocci.
663
Many centers add vancomycin empirically for all neutropenic bone marrow transplant patients at onset of fever.
Vancomycin should also be added empirically for nosocomial neutropenic fever if incidence of methicillin-resistant Staphylococcus aureus (MRSA) is high (>5%) in your
facility.
Add acyclovir if cold sores or HSV-appearing lesions are
present.
Add anaerobic coverage (metronidazole, clindamycin, imipenem-cilastatin) if abdominal pain is consistent with typhlitis
(right lower or right upper quadrant tenderness on palpation).
Add oral fluconazole if patient has oral thrush.
Admit patient to monitored bed if systolic blood pressure is
<100 mm Hg.
Neutropenic patients do not manifest typical signs of sepsis and require close monitoring.
Tunnel infections at site of indwelling catheter require
removal of the line.
Some line infections can be treated through the line without removal (Staphylococcus epidermidis).
Consult hematology or infectious disease for assistance if
line culture is positive.
If patient remains febrile without a source, consider what
infections the antibiotics are not coveringpossible
abscess, viral infection (HSV, varicella-zoster virus),
MRSA, Clostridium difficile, atypical bacteria, anaerobes,
Pneumocystis carinii pneumonia, fungal infections.
If patient remains febrile without source on hospital day
4-5, add empiric antifungal coverage to cover Candida and
Aspergillus (amphotericin, 1 mg/kg)
Fulminant sepsis >3-6 hours despite appropriate antibiotics
should raise suspicion of Clostridium septicum.
Start anaerobic antibiotic coverage (metronidazole, clindamycin, imipenem-cilastatin) and perform physical exam
to identify possible site of necrotizing fasciitis requiring
surgical debridement.
If possible source of infection is identified, add specific
antibiotic coverage for that infection but do not narrow broadspectrum coverage.
Continue to reculture at least once every 24 hours if patient
remains febrile.
664
III DISEASES
Use of Growth Factors in Neutropenic Fever
The value of routine use of growth factors (i.e., G-CSF, GMCSF) is debatable and they cannot be recommended at this
time.
Primary effectto shorten the duration of neutropenia or
hospitalization by approximately 24 hours without affecting mortality
Consult a hematologist before initiating growth factor
therapy.
665
III DISEASES
PANCREATITIS
Suresh T. Chari, M.D.
DEFINITION AND PATHOGENESIS

Acute or chronic inflammatory process of the pancreas, with
variable involvement of other regional tissues or remote
organ systems
Pathogenetic mechanisms are not fully understood.
Acute and chronic pancreatitis appear to involve different
pathophysiologic processes (Table 1).
In most cases, acute pancreatitis probably does not lead to
chronic pancreatitis.
Currently, the acute and chronic forms are differentiated
on the basis of radiographic and histologic features.
Acute and chronic pancreatitis are compared in Table 2.
ACUTE PANCREATITIS
Etiology
The etiology of acute pancreatitis is outlined in Table 3.
EPIDEMIOLOGY
Incidence4.8-24.2/100,000
Incidence increases with age (peak age, 50-60 years).
Gallstone diseasemore common in women
Alcoholic diseasemore common in men
Threefold more common in black men than white men
The signs, symptoms, and severity of acute pancreatitis are
listed in Tables 4, 5, and 6, respectively.
Special abbreviations used in this chapter: APACHE, acute physiologic assessment and chronic health evaluation; ERCP, endoscopic retrograde cholangiopancreatography.
667
Table 1. Pathophysiology of Acute and Chronic

Pancreatitis
Acute
pancreatitis
Chronic
pancreatitis
Presumed
initiating
event
Inappropriate intraIncompletely understood

pancreatic activation Hypotheses include:
of zymogens
Duct obstruction due to
protein plugs
Toxic effects of chronic
alcohol use
Repeated episodes of
pancreatitis lead to
chronic scarring
(necrosis-fibrosis
sequence)
Aggravating Ischemia (transforIschemia, free radicals,
events
mation from mild
immune-mediated insult
edematous pancreatitis to severe
necrotizing form)
Pancreatic
Normal before attack Usually associated with permorphology Unless parenchyma
manent, often progressive,
is lost from necrosis, alteration in pancreatic
structure returns to
structure
normal after panChanges include varying
creatitis resolves
degrees of edema, acute
inflammation, & necrosis
superimposed on chronic
changes, e.g., fibrosis,
inflammation, loss of
exocrine tissue
Complications
Acute complications are listed in Table 7.
Acute pancreatitis can be suspected clinically.
Confirmation requires biochemical or radiologic evidence.
All features must be considered together.
Clinical
Acute upper abdominal pain
668
III DISEASES
Table 2. Comparison of Features of Acute and Chronic
Pancreatitis
Acute
Etiology (most
common)
Epidemiology
Alcohol, gallstones
Common diagnostic
tests
Amylase/lipase, CT
Management
Pain management
Fluids
Removal of precipitating factors (e.g.,
common bile duct
stone)
Common complications
Localnecrosis &
infection
Pancreatic fluid
collections
Systemicorgan
failure
Excellent if mild
disease
High morbidity/
mortality if necrotizing, especially
if infected
Men, women
Age: 50-60s
Clinical presentation Acute abdominal
pain
Prognosis
Chronic
Alcohol
Men
Age: 35-45
Abdominal pain can
be recurrent, continuous, or absent
Abdominal X-ray, CT,
ERCP, pancreatic
function tests
Alcohol abstinence
Pain management
Treatment of pancreatic insufficiency
(endocrine/exocrine)
Treatment of complications
Pseudocysts
Bile duct or duodenal
obstruction
Good long-term
survival
High morbidity due to
complications
Death often a complication of chronic
alcohol & tobacco
abuse
ERCP, endoscopic retrograde cholangiopancreatography.
669
Table 3. Etiology of Acute Pancreatitis*

Obstruction
Toxins
Drugs
Definite
Gallstones, biliary sludge, microlithiasis

Ampullary or pancreatic tumors (primary or
metastatic)
Less commonpancreas divisum with
accessory-duct obstruction, choledochocele,
periampullary duodenal diverticula, hypertensive
sphincter of Oddi, worms or foreign bodies
(occluded pancreatic duct stent) obstructing
papilla
Ethanol, methyl alcohol, scorpion venom,
organophosphorus insecticides
Didanosine, pentamidine, metronidazole,

stibogluconate, sulfonamides, tetracycline,
furosemide, thiazides, sulfasalazine, 5-ASA,
azathioprine, 6-mercaptopurine, valproic acid,
L-asparaginase, sulindac, salicylates, calcium,
estrogen, tamoxifen
Probable
Nitrofurantoin, ethacrynic acid, diazoxide,
warfarin, cimetidine, ranitidine, quinidine, acetaminophen, ACE inhibitors, methyldopa, clonidine
Metabolic
Hypertriglyceridemia (hyperlipoproteinemia
abnormalities types I, II, VI or acquired causes, e.g., poorly
controlled diabetes mellitus, obesity, druginduced, nephrotic syndrome, hypothyroidism,
pregnancy, glucocorticoid excess)
Hypercalcemia
Infectious
Parasitic
Ascariasis, clonorchiasis, toxoplasmosis,
cryptosporidiosis
Viral
Mumps, rubella, hepatitis A & B, coxsackievirus,
echovirus, adenovirus, CMV, HSV, varicella,
EBV, HIV
Bacterial
Mycoplasma, Campylobacter jejuni,
Mycobacterium tuberculosis, M. avium
complex, Legionella, Leptospira, Salmonella
Fungal
Aspergillus
Inherited
Pancreas divisum, choledochocele type V,
hereditary gene mutations
Vascular
Ischemic pancreatitis (e.g., postoperative
abnormalities hypoperfusion)
Atherosclerotic emboli
Vasculitis (SLE, polyarteritis nodosa, malignant
hypertension)
670
III DISEASES
Table 3 (continued)
Trauma
Accidental
Iatrogenic
Miscellaneous
Blunt or penetrating trauma to abdomen

Post-ERCP (especially after therapeutic
intervention or manometry of sphincter of Oddi),
postoperative
Penetrating peptic ulcer, Crohn disease, renal
transplantation
Idiopathic
ACE, angiotensin-converting enzyme; CMV, cytomegalovirus; EBV, EpsteinBarr virus; ERCP, endoscopic retrograde cholangiopancratography; HSV,
herpes simplex virus.
*Gallstones and ethanol abuse account for 75% of cases.
Items in bold are common causes for the category.
Biochemical
Many tests are available but none has proved superior to
amylase or lipase for diagnosis, although pancreatic
isoamylase has the best sensitivity and specificity of all
markers (Table 8).
For etiologic determination:
ALT 3-fold increase from baseline specific for
biliary pancreatitis
Serum triglyceridesusually >1,000 mg/dL to cause
pancreatitis
Serum calciumshould be repeated after resolution of
attack to avoid false-negative results
Biochemical tests available are listed in Table 9.
For prognostic evalulationCBC, fasting glucose, LDH,
AST, BUN, serum calcium, arterial blood gases (see Ranson
criteria below)
Imagingcrucial for confirming diagnosis and determining cause
Plain films
Inexpensive and easy to obtain at bedside if necessary
Useful for ruling out life-threatening causes of abdominal pain, e.g., bowel obstruction or perforation
671
Findings are nonspecific, and additional testing is usually needed.

Abdominal X-rayFindings are normal in mild disease; sentinel loop (small-bowel ileus) or colon cutoff sign (descending colon spasm due to severe inflammation) or diffuse ileus seen in severe disease.
Chest X-rayFindings are abnormal in about 1/3 of
patients and include elevation of hemidiaphragm, pleural effusions, basal atelectasis, pulmonary infiltrates,
and acute respiratory distress syndrome.
Table 4. Signs of Acute Pancreatitis

Systemic features
Abdominal exam
Fever, tachycardia; in severe cases, even

shock and coma
Jaundice (if obstruction present)
Mildepigastric tenderness
Severeabdominal distension (especially
epigastric), tenderness, guarding
Dyspnea, shallow breathing, pleural effusions
Grey Turner sign (flank ecchymosis), Cullen
sign (periumbilical ecchymosis)
Respiratory
Hemorrhagic
complications
(uncommon)
Miscellaneous (rare) Epigastric palpable mass (pseudocyst),
SQ evidence of fat necrosis (panniculitis),
thrombophlebitis of lower extremities,
polyarthritis
Table 5. Symptoms of Acute Pancreatitis

Acute abdominal pain (90%-95% of patients)
Qualitysteady
Locationmidepigastrium, right upper quadrant, diffuse, left
upper quadrant
Durationup to days
Radiationbandlike with radiation to back (50% of patients)
Provocative factorspostprandial (biliary), alcohol binge/
cessation (alcoholic)
Relieving factorsbending forward and/or sitting upright
Nausea and vomiting (90% of patients)
Restlessness, agitation
672
III DISEASES
Table 6. Severity of Acute Pancreatitis
Mild
Severe
Minimal or no organ dysfunction

No local complications
Uneventful recovery
Manifests as organ failure and/or local complications
(e.g., necrosis, abscess, or pseudocyst)
3 of Ransons 11 criteria present
APACHE-II score >8
APACHE, acute physiologic assessment and chronic health evaluation.
Table 7. Acute Complications of Pancreatitis

Local
Pancreatic necrosis
sterile or infected
Pancreatic-fluid collectionspseudocysts or
abscesses
Bowel necrosis & necrotizing obstruction or
fistulization of colon
GI hemorrhageulceration, gastric varices,
rupture of pseudoaneurysm
Splenic vein thrombosis
Splenic rupture or
hematoma
Hydronephrosis &
hydroureter
Systemic
Shock
SQ nodules
Coagulopathy
Respiratory
failure &
ARDS
Acute renal
failure
Purtscher angiopathic
retinopathy & acute
blindness
Pancreatic
encephalopathy
Hyperglycemia
Hypocalcemia
ARDS, acute respiratory distress syndrome; GI, gastrointestinal.
Ultrasound
Not used routinely for diagnosisBowel gas obscures
imaging of pancreas in 1/3 of patients, leading to incomplete examination.
Sensitive method for evaluating gallbladder, not as sensitive for common bile duct stones
Classic findingdiffusely enlarged, hypoechogenic
pancreas.
673
Table 8. Current Diagnostic Approach

Test
Amylase
Lipase
Pancreatic
isoamylase
Urinary
amylase
674
Comments
Increase 3 times upper limit of normal, cornerstone of diagnosis; returns to normal faster than
lipase levels
Many nonpancreatic diseases can also cause
increased serum levels, especially <3 times
elevated
Combine with clinical and radiologic features for
diagnosis
Somewhat greater sensitivity & specificity than
amylase
Many nonpancreatic causes for elevation
Useful for late presentation to physician
Combination of amylase & lipase does not seem
to improve diagnostic accuracy
No prognostic role for serial measurement
If amylase is increased without increase in lipase
on repeated testing, consider macroamylasemia or
nonpancreatic amylase increase
Not commonly ordered despite apparent superiority
Useful when suspecting nonpancreatic amylase
increase
Does not usually add important diagnostic
information to serum enzyme levels except in
macroamylasemia
CT
Most important test for diagnosis of acute pancreatitis
and intra-abdominal complications and for assessment
of severity of disease (see Balthazar-Ranson CT Severity
Index below).
In mild disease, CT may be normal.
All patients whose condition is not improving or who
have suspected complications should have CT.
Contrast-enhanced CTgold standard for noninvasive
diagnosis of pancreatic necrosis (necrosis may not be
apparent on CT in the first 24 to 48 hours after onset of
pancreatitis)
If infection is suspected, CT-guided aspiration can differentiate sterile pancreatic necrosis from infected
necrosis.
III DISEASES
Table 9. Biochemical Tests Available
Condition
Increased serum & urinary
levels of pancreatic enzymes
Increased serum levels of
nonenzymatic pancreatic
secretion
Severity markers
Tests
Amylase, pancreatic isoamylase,
lipase not clinically used
Pancreatitis-associated protein,
trypsinogen activation peptide
Hematocrit, C-reactive protein
Findingsedematous pancreas, areas of necrosis, peripancreatic inflammation, acute fluid collections, pseudocysts, abscess, hemorrhage into pancreas and surrounding areas
MRI and magnetic resonance cholangiopancreatography
Increasing role in diagnosis and management of pancreatitis
Images are equal or superior to those of CT, without
nephrotoxicity of contrast or invasive technique of endoscopic retrograde cholangiopancreatography (ERCP).
Limitationshigher cost and operator dependence
ERCP
Diagnosis and treatment of common bile duct stones
Role when no definite cause of pancreatitis is found
after initial investigation
Abnormalities shownsmall pancreatic tumors, pancreatic ductal strictures, gallstones, pancreas divisum,
choledochocele, hypertensive sphincter of Oddi.
MANAGEMENT
Mild Acute Pancreatitis
Supportive care
IV fluids
Generous fluid resuscitation because of third space loss,
vomiting, diaphoresis
No magic numbers, use clinical variables to guide
amount of fluid.
675
Pain controlparenteral narcotics usually required

Fentanyl, morphine, meperidine, hydromorphone can be
used (see Severe Acute Pancreatitis below)
Oral intake is encouraged early and advanced from clear
liquid diet to solid food as tolerated. Routine nasogastric
tube is not necessary or beneficial (use only for gastric or
intestinal ileus or intractable nausea and vomiting).
Removal or management of factors that may have precipitated attackcessation of alcohol use, cessation of
drugs, insulin for poorly controlled diabetes with hypertriglyceridemia, reversal of hypercalcemia, early ERCP
when indicated for gallstone disease (see Special
ConsiderationsGallstone Pancreatitis below)
Not indicatedproton pump inhibitors or H2-receptor
blockers, prophylactic antibiotics
Severe Acute Pancreatitis

ICU monitoring
Fluid resuscitation
May need 5-10 L of fluid (normal saline or Ringer lactate) daily
Goalkeep hematocrit approximately 30%, may need
packed RBCs if <30%
Unstable cardiovascular and pulmonary states may benefit from Swan-Ganz catheter placement to help guide fluid
resuscitation.
Pain controlIV narcotics, usually patient-controlled
analgesia.
Fentanyl preferred
Hydromorphone for more severe pain
Morphine, despite theoretical increase in sphincter of Oddi
pressure, no evidence of aggravating or causing pancreatitis
or cholecystitis
Meperidine can be used but should be avoided because
potentially toxic metabolites accumulate.
Multiorgan support
Respiratory
Oxygen for saturation <95% by nasal prongs or face mask
Endotracheal intubation and assisted ventilation (in
case of failure to correct hypoxemia or fatigue/respiratory insufficiency)
676
III DISEASES
Acute respiratory distress syndrome (serious complication)endotracheal intubation with positive endexpiratory pressure ventilation and low tidal volume
Cardiovascular
Complications such as congestive heart failure, acute
myocardial infarction, arrhythmias, cardiogenic shock
Hypotension refractory to fluid resuscitationdopamine
drip
Renal
Monitor urine outputadequate marker for tissue
perfusion
Aggressive fluid resuscitation to prevent acute renal
tubular necrosis
Metabolic
Hyperglycemiacareful use of insulin (variable blood
glucose with ongoing inflammation)
Hypocalcemiaonly if decreased ionized calcium, supplementation with calcium gluconate/chloride
HypomagnesemiaSupplementation may be enough to
avoid symptomatic hypocalcemia.
Prevention of infectionIV prophylactic systemic antibiotics
Imipenem-cilastatin, quinolones, third-generation
cephalosporins, piperacillin, mezlocillin, metronidazole
Prophylactic therapy for 5-10 days; after that, continue
only if documented infection
Role for prophylactic antifungals is not clear, not routinely recommended.
Treatment of pancreatic necrosis
If sterile, no specific intervention is required
If infected, debridement (percutaneous, surgical, endoscopic) may be required.
Surgery consultation is recommended.
Usual approach is to initiate antibiotics once necrosis
involving >30% pancreatic tissue is diagnosed by CT.
If no improvement after 1 week, perform CT-guided
aspiration and necrosectomy or other debridement techniques if infection is present.
677
If sterile, continue medical therapy for 4-6 weeks

(patients usually do well medically).
If suspicion for infection is high, consider repeating
aspiration.
Nutrition
Make every attempt to give enteral nutrition whenever
possible to maintain intestinal barrier, to decrease bacterial translocation, and to avoid metabolic and catheterrelated infectious complications associated with total
parenteral nutrition.
Because of intolerance to oral intake, such patients usually
require placement of jejunal feeding tube, either endoscopically or radiologically.
If goal rate is not achieved within 48-72 hours, provide
supplemental parenteral nutrition.
Refeeding should be gradual once appetite returns and should
not be dictated by lab studies such as CBC or amylase levels.
Not proved to be beneficialoctreotide, somatostatin, calcitonin, gabexate mesilate, aprotinin, nasogastric decompression, H2-receptor antagonists, anticholinergics, glucagon,
fresh frozen plasma, peritoneal lavage
Special ConsiderationsGallstone Pancreatitis

Early ERCP and papillotomy for patients with severe acute
biliary pancreatitis with obstructive jaundice (bilirubin >5
mg/dL) or cholangitis
For patients without cholangitis or biliary obstruction, elective cholangiography (magnetic resonance cholangiopancreatography or intraoperative cholangiography) should be
performed to exclude residual nonobstructing bile duct stones.
Cholecystectomyafter recovery and preferably before hospital discharge for all patients with gallstone pancreatitis
(delay of approximately 7 days for mild and at least 3 weeks
for severe pancreatitis is reasonable)
COURSE AND PROGNOSIS
Most attacks are mild; recovery is within 5-7 days. Death is
unusual.
Daily amylase or lipase tests to follow course of pancreatitis
are not helpful. Patients condition can worsen despite
improving enzyme levels.
678
III DISEASES
Severe necrotizing pancreatitishigh rate of complications

and marked mortality, especially when infection is present
Risk of infectionincreases with amount of necrosis and
time from onset of acute pancreatitis (peaks at 3 weeks)
Overall mortality in necrotizing pancreatitis, up to 30%.
Early deaths (<2 weeks) usually are due to severe systemic inflammatory response and multisystem failure.
Late deaths are due to local or systemic infections; 80%
of these deaths are due to infected necrotizing pancreatitis.
Mortality of infected necrotizing pancreatitis is approximately
30% compared with 10% for sterile necrotizing pancreatitis.
Grading systems that combine clinical and lab data have
been proposed to indicate the severity of pancreatitis and
identify patients at risk for complications.
The most useful in practice are the Ranson criteria and
acute physiologic assessment and chronic health evaluation (APACHE) II scores.
Ranson criteria are based on 11 clinical signs with prognostic importance (Table 10).
APACHE II is based on 12 physiologic variables, patient
age, and any history of severe organ-system insufficiency or immunocompromised state.
Advantages of APACHE II over Ranson criteria
Can be used not only within first 48 hours after admission but throughout hospitalization
May be the most accurate predictor of disease severity
CT grading systemBalthazar-Ranson CT Severity Index
(Table 11)
CT is probably the most helpful way to assess severity of
acute pancreatitis, particularly when the results are combined with clinical scores.
CHRONIC PANCREATITIS
Classification
Chronic calcifying pancreatitisprogressive disorder characterized by calcification and failure of pancreatic function,
often despite removal of offending agent (e.g., abstinence
in alcohol-induced pancreatitis)
679
680
Table 10. Ranson Criteria for Predicting Severity of Acute Pancreatitis*

Non-gallstone pancreatitis
0 hour
Age >55
WBC >16 109/L
Blood glucose >200 mg/dL
LDH >350 U/L
AST >250 U/L
48 hours
Hematocrit by 10%
BUN 5 mg/dL despite
fluids
Serum Ca <8 mg/dL
pO2 <60 torr
Base deficit >4 mEq/L
Fluid deficit >6 L
0 hour
Gallstone pancreatitis
48 hours
Age >70
WBC >18 109/L
Blood glucose >220 mg/dL
LDH >400 U/L
AST >250 U/L
*Presence of 1 or 2 criteria, mortality <1%; 3 or 4 criteria, 15%; 6 or 7 criteria, 100%.
Hematocrit by 10%
BUN 2 mg/dL despite
fluids
Serum Ca <8 mg/dL
Base deficit >4 mEq/L
Fluid deficit >4 L
III DISEASES
Chronic obstructive pancreatitisresult of pancreatic duct

obstruction by any cause
Does not calcify
Cured by relief of obstruction
Etiology
The causes of chronic pancreatitis are listed in Table 12.
Epidemiology
True prevalencenot known
Incidence3-9/100,000
Peak incidence35-45 years
Alcoholic diseasemore common in men
Table 11. Balthazar-Ranson CT Severity Index (CTSI)*

Grading based on findings on unenhanced CT
Grade
Findings
A
Normal pancreasnormal size, sharply
defined, smooth contour, homogeneous
enhancement, retroperitoneal peripancreatic fat without enhancement
B
Focal or diffuse enlargement of pancreas,
contour may show irregularity, enhancement may be inhomogeneous but
there is no peripancreatic inflammation
C
Peripancreatic inflammation with
intrinsic pancreatic abnormalities
D
Intrapancreatic or extrapancreatic fluid
collections
E
Two or more large collections of gas in
pancreas or retroperitoneum
Necrosis score based on contrast-enhanced CT
Necrosis, %
0
<33
33-50
>50
Score
0
2
3
4
0
2
4
6
*CTSI = unenhanced CT score + necrosis score (maximum = 10). Severe
disease 6.
681
Table 12. Causes of Chronic Pancreatitis

Chronic calcifying pancreatitis*
Chronic alcohol use
Hereditary pancreatitis
Tropical pancreatitis
Metabolic diseases (hyperlipidemia, primary hyperparathyroidism)
Autoimmune (primary or associated with Sjgren syndrome,
PSC, IBD)
Idiopathic
Chronic obstructive pancreatitis
Ductal obstruction (posttraumatic & postpancreatitis
strictures, periampullary tumors, intraductal tumors)
IBD, inflammatory bowel disease; PSC, primary sclerosing cholangitis.
*Alcohol abuse accounts for 70%-90% of cases.
Signs and Symptoms
Abdominal pain
Characteristics similar to those of acute pancreatitis
Early in disease course, may occur in discrete attacks but
progressively tends to become more continuous
Absent in approximately 15% of cases
Findings may include epigastric or upper abdominal tenderness, fever, and epigastric mass (pseudocyst).
Pancreatic insufficiency
Exocrine
Loss of >90% of pancreatic parenchyma leads to steatorrhea with malabsorption of fat, protein, and carbohydrates and malabsorption of vitamin B12 and fat-soluble vitamins.
Weight loss is usually prominent.
Endocrine
With >90% loss of tissue, glucose intolerance occurs.
Overt diabetes is rare, usually occurs in advanced
disease.
Diagnosis
Biochemical and imaging tests are listed in Tables 13 and
14, respectively.
682
III DISEASES
Complications
Complications of chronic pancreatitis are listed in Table 15.
Management
Generalabstinence from alcohol or other causative agents
Pain managementguidelines recommend following stepwise approach:
Look for treatable causes of pain (e.g., pseudocyst) or
pain unrelated to pancreatitis.
Abstinence from alcohol, nonnarcotics for pain
Eight-week trial of high-dose oral pancreatic enzymes with
acid suppression (proton pump inhibitor or H2-antagonists)
Consider celiac plexus block
Consider endoscopic treatment (preliminary evidence
for endoscopic procedures, sphincterotomy, lithotripsy,
pancreatic duct stenting)At this point, consider narcotics and surgery.
Table 13. Biochemical Tests for Chronic Pancreatitis

Test
Amylase &
lipase
Liver function
tests
72-Hour fecal
fat
Pancreatic
function tests
Comments
Usually increased levels during acute flares but
may be normal or only slightly elevated
May be abnormal from alcoholic liver disease
May be abnormal in 5%-10% of patients with
intrapancreatic bile duct obstruction (edema/
fibrosis)
Increased if exocrine insufficiency present
Useful in cases of recurrent pain & negative
imaging studies
Negative results do not exclude chronic
pancreatitis
Usually done in combination with ERCP or
endoscopic ultrasonography
Most sensitive is secretin or CCK-stimulated
pancreatic function test (requires approximately
60%-70% of tissue loss)
CCK, cholecystokinin; ERCP, endoscopic retrograde cholangiopancreatography.

683
Table 14. Imaging Tests for Chronic Pancreatitis

Test
Plain abdominal
X-rays
Transabdominal
ultrasound
CT
MRI/MRCP
ERCP
Endoscopic
ultrasound
Comments
Pancreatic calcifications (within ductal system,
not in parenchyma) pathognomonic, present
in up to 30% of cases
Pancreatic enlargement, ductal dilatation,
pseudocyst
Best noninvasive test
May show calcifications & cysts not seen on
plain X-rays
Still under investigation
Calcification often not seen
Gold-standard for imaging diagnosis
Not usually first test done
Operator dependent
Picks up subtle changes in gland not seen on
ERCP
Role being evaluated
ERCP, endoscopic retrograde cholangiopancreatography; MRCP, magnetic

resonance cholangiopancreatography.
Usually short-term use of narcotics (preferably, long-acting fentanyl or morphine [MS Contin])
Reserve surgical treatment for patients with severe pain not
responsive to lesser tactics.
If duct dilatation is present (>6 mm)surgical decompression and drainage (e.g., lateral pancreaticojejunostomy or Peustow procedure)
If absentnerve ablation (unilateral or bilateral thoracoscopic splanchnic nerve resection or percutaneous
celiac nerve block) or pancreatic resection (partial or
complete, with or without pylorus and duodenum
preservation)
Treatment of complications
PO pancreatic enzyme replacement for fat malabsorption
Resection, external drainage or internal drainage for
pseudocysts that persist for >6 weeks, have signs of infection, or are rapidly enlarging or causing symptoms
ERCP with stenting of pancreatic duct leak for pancreatic ascites and pleural fistulas
684
III DISEASES
Table 15. Complications of Chronic Pancreatitis
Pseudocysts
Pancreatic ascites &
pleural effusion
Hemosuccus
pancreaticus
Pancreatic cancer
Splenic vein
thrombosis
Bile duct or duodenal
obstruction
Pseudoaneurysm
Endocrine
insufficiency
Exocrine
insufficiency
Narcotic addiction
Relief of obstruction by pseudocyst decompression, endoscopic stenting, or surgical procedure for symptomatic
bile duct or duodenal obstruction
Course and Prognosis

Chronic pancreatitis leads to structural damage of pancreas
and progressive loss of parenchymal tissue.
Chronic pain and exocrine and endocrine dysfunction may
result.
Association with pancreatic cancerdevelops in about 4%
of patients within 20 years, more frequent with tropical and
hereditary pancreatitis
Associated with various complications, of which pseudocyst and duodenal or bile duct obstruction are the most
common
Abstinence from alcohol may reduce frequency and severity of attacks.
It also reduces risk of dying of alcohol-related nonpancreatic disease.
Mortality
Related mostly to lethal effects of alcohol and tobacco
use
About 15%-20% of patients die of complications of chronic pancreatitis.
685
III DISEASES
PERICARDIAL DISEASES
James B. Seward, M.D.
DEFINITIONS
Acute pericarditisacute, painful inflammation of the pericardium that usually results in mild to moderate pericardial
effusion
Effusive-constrictive pericarditisrecurring bouts of acute
pericarditis that eventually cause pericardial thickening and
constrictive physiology
Constrictive pericarditischronic pericarditis that causes
global or localized thickening and loss of elasticity of the
pericardium, with or without calcification, that leads to
impaired ventricular filling and high intracavitary pressures,
resulting in a syndrome of right-sided heart failure
Pericardial effusionabnormal amount of fluid in the
pericardial space (>50 mL)
Pericardial tamponadeacute hemodynamic compromise
consisting of increased end-diastolic pressures, impediment
to ventricular filling with low cardiac output, as a result of
rapid and/or severe accumulation of pericardial effusion
causing high intrapericardial pressures.
TYPES AND CAUSES OF PERICARDIAL DISEASE
The types of pericardial diseases and their causes are listed
in Table 1.
Acute Pericarditis
Clinical Setting
Suspect acute pericarditis in patients who have
Low risk factor profile for coronary disease
Acute febrile illness
687
688
Table 1. Types and Causes of Pericardial Disease

Type
Idiopathic
Viral
Cause
Up to 30% of cases
Coxsackievirus, influenza,
hepatitis A & B, HIV,
enterovirus
Bacterial
Staphylococci, streptococci, pneumococci,
gram-negative bacteria
Mycobacterial TB
Fungal
Histoplasma, coccidiodomycosis, Candida,
Aspergillus
Metabolic/
Uremia, hypothyroidism,
hemodynamic adrenal insufficiency,
CHF, hypoalbuminemic
states
Rheumatologic Rheumatoid arthritis, SLE,
scleroderma, Wegener
granulomatosis,
sarcoidosis
Tamponade
Acute symptoms
Effusion size
Constriction
Very common
Very common
Small/moderate
Small/moderate
Very rare
Very rare
Almost never
Almost never
Infrequent
Variable
Common with
staphylococci
Uncommon but
possible
Rare
Variable
Variable
Variable
Very common
Uncommon
Rare
Uncommon
Rare but common

with uremia
Variable
Never
Possible with
uremia
Rare but common

with SLE
Small but may be

large with SLE
Rare
Rare but possible

with SLE
Table 1 (continued)
Type
Cause
Acute symptoms
Effusion size
Constriction
Tamponade
Postcardiotomy syndrome, Common postoperaMI, radiation, blunt or

tive cardiac and
perforating trauma,
post MI
aortic dissection,
esophageal fistula
Variable
Uncommon, but
common with
radiation
Neoplastic
Primary tumors of
pericardium (sarcoma,
mesothelioma),
metastatic tumors
(renal cell, melanoma,
lymphoma)
Hydralazine, procainamide, amiodarone
(drug-induced lupus)
Uncommon
Large
Rare
Rare with
Dressler syndrome &
radiation, but
common with
dissection, myocardial rupture
Common
Uncommon
Small to
moderate
Rare
Rare
Drugs
CHF, congestive heart failure; MI, myocardial infarction; SLE, systemic lupus erythematosus.
689
III DISEASES
Traumatic
Chest pain in the setting of another disease, e.g., upper

respiratory tract illness, florid connective tissue disease,
acute uremia
Symptoms
Fevers
Chest pain, pleuritic componentworsens in supine position
and is relieved with leaning forward, may be indistinguishable from anginal pain
Signs
Tachycardia
85% of patients have pericardial rubs.
Atrial arrhythmias are not uncommon.
Increase in jugular venous pressure depends on the physiologic significance of the effusion rather than on the size and
should alert you to the possibility of tamponade.
Distant heart sounds in very large effusions
Pericardial Tamponade
Clinical Setting
Suspect tamponade in patients who
Acutely decompensate days after myocardial infarction
(free wall rupture)
Have sudden onset of hypotension with high central venous
pressure in the early post cardiac surgery period in the
ICU
Have metastatic malignancy
Have had TB or systemic lupus erythematosus
Have aortic dissection or known thoracic aortic aneurysm
Remember that the effusion does not need to be large for
tamponade to occur: small effusions that develop in minutes
to hours (e.g., myocardial puncture during right ventricular
biopsy), very large effusions that develop over weeks to
months (e.g., neoplastic effusions).
Symptoms
Dyspnea is the main and most often the only complaint.
Occasionally chest pressure or heaviness
Light-headedness when progression is slow
690
III DISEASES
Signs
Tachycardia is universal.
Most patients are hypotensive or relatively hypotensive
compared with previous measurements of their blood pressure.
Extremities are cold.
Jugular venous pressure is invariably elevated.
Tachypnea with borderline oxygen saturation
Edema is present only if tamponade has been a very slow
process.
Fourth heart sound is usually present.
Distant heart sounds are present only if progression is slow
and effusion is very large.
Pulsus paradoxus is the classic sign but is insensitive and a
very late preterminal finding.
Constrictive Pericarditis
Clinical Setting
Suspect constriction in patients who
Present with predominant right-sided heart failure
Had previous cardiac surgery
Present years after having radiotherapy to the chest
Have had several bouts of pericarditis in the past (effusive-constrictive)
Become rapidly prerenal when placed on diuretics without
proportional fluid loss
Had TB
Symptoms
Progressive dyspnea
Increased abdominal girth
Lower extremity swelling
Signs
Increased central venous pressure
Prominent x and y descent on jugular venous pulsations
Kussmaul sign (increased jugular venous pressure with
inspiration)
Pericardial rub (15% of patients)
691
Ascites
Lower extremity edema
Pericardial knock (protodiastolic dull sound, like a third
heart sound but heard best in the left sternal border)
DIAGNOSTIC TESTS
Acute Pericarditis
Echocardiography
Diagnostic gold standard in the right clinical setting
Pericardial effusion
Sunburst pattern of the pericardium (in pericarditis without effusion)
Lab Exam (Low Specificity, Low Sensitivity)
Increased number of WBCs with lymphocytosis
Increased ESR and C-reactive protein
Mildly increased levels of cardiac enzymes
Markers of other diseasesBUN, creatinine, antinuclear
antibody, rheumatoid factor, antineutrophil cytoplasmic
antibody, etc.
ECG (Low Sensitivity, Moderate Specificity)

Sinus tachycardia or atrial arrhythmias (i.e., atrial fibrillation
or flutter)
Diffuse ST-segment elevation
In all walls
If in contiguous leads, suspect myocardial infarction or
myocarditis.
PR depression in inferolateral leads (II, III, aVF, V , V )
5 6
Low voltage (in large effusion, insensitive)
Electrical alternans (in very large effusions)
Absence of Q waves, peaked T waves
Radiology
Chest X-ray shows globular heart (low sensitivity, low
specificity).
CT of chest shows effusion (good sensitivity, useful to rule
out other causes of chest pain, e.g., pneumonia, dissection,
pulmonary embolism)
692
III DISEASES
Cardiac Tamponade
Echocardiography
The gold standard and only test necessary
Pericardial effusion is usually circumferential but may be
localized in patients after cardiac surgery.
Right ventricular diastolic collapse (very specific, but may
be insensitive in patients with very high right ventricular
pressures, i.e., pulmonary hypertension)
Atrial diastolic collapse (very sensitive but not very specific
because it may occur in patients with normal hemodynamics)
More than 25% respiratory variation of Doppler transmitral
inflow velocities or >50% variation across the tricuspid valve
(moderate sensitivity and good specificity)
Hepatic vein and inferior vena cava dilatation with lack of
inspiratory collapse (sensitive but not specific, has a high
negative predictive value, i.e., if absent, makes tamponade
unlikely even in the setting of a large effusion)
Lab Exam, ECG, Chest X-Ray
No role in the diagnosis of tamponadedo not waste time!
Echocardiography
The gold standard
Respiratory septal displacement with ventricular interdependence (sensitive and good specificity)
Thickened or calcified pericardium (insensitive)
Lab Exam and ECG
Not helpful in the diagnosis
Radiology
CT may show thickened pericardium (specificity increases
with pericardial thickness and microcalcification).
Chest X-ray, second-most helpful examination, may show pericardial calcification in 25% of cases.
MRI shows thickened pericardium (will not show calcium).
Constriction can occur with a normal pericardial thickness
693
Right and Left Heart Catheterization

Only performed if necessary after echocardiography
Ventricular interdependence (sensitive and specific)
End-diastolic pressure equalization between the left and right
ventricles (sensitive but not specific)
Rapid descent, rapid increase, and plateauing of right ventricular diastolic pressure (square root sign)
Prominent x and y descent on right atrial tracing
The main difficulty in the diagnosis of constrictive pericarditis is differentiating it from restrictive cardiomyopathy.
It is usually necessary to use echocardiographic, hemodynamic, and radiologic data to establish either diagnosis.
At times, the diagnosis of constriction is so elusive that it
can be confirmed only at surgery.
MANAGEMENT
Acute Pericarditis
Idiopathic
ViralNSAIDs
Bacterialantibiotics with percutaneous or surgical drainage
and pericardiectomy in some cases
Inadequate treatment may lead to constriction.
Systemic lupus erythematosus, rheumatoid arthritiscorticosteroids
Effusions due to scleroderma do not respond to corticosteroids.
Post-pericardiotomy syndromecorticosteroids
Dressler (late post-myocardial infarction) syndromecorticosteroids or NSAIDs
Early post-myocardial infarction revascularization
Avoid NSAIDs and corticosteroids for a week because they
are associated with increased risk of myocardial rupture.
Uremiadialysis
Hypothyroidismthyroid hormone replacement
Tamponade
Treatment is emergency echocardiography-guided pericardiocentesis for immediate pericardial decompression.
Long-term strategy depends on the cause:
Malignantprolonged drainage, window infrequently
necessary
694
III DISEASES
Traumaticsurgical correction of trauma (i.e., dissection, rupture, perforation)

Inflammatorypericardiocentesis with pigtail catheter
and treatment of underlying disease
Surgical pericardiectomy
Surgical risk moderate
Total pericardiectomy preferred
Nerve injury complication (phrenic)
695
III DISEASES
PNEUMONIA
DEFINITION
Pneumoniacough, fever, and new infiltrate on chest Xray (regardless of sputum production)
Nosocomial pneumonianew pulmonary infiltrate and fever
developing after 48 hours of hospitalization
CLASSIFICATION AND ETIOLOGY
Community-Acquired Pneumonia
Typical and atypical usually refer to organism causing
disease; there is loose association with presentation (see below).
Typical
Streptococcus pneumoniae most common (including AIDS)
Other organismsHaemophilus influenzae, Moraxella
catarrhalis; occasionally Klebsiella sp or Staphylococcus
aureus
Atypical
Mycoplasma pneumoniae or Chlamydia pneumoniae (previously healthy, young)
Legionella spp (elderly smoker)
Viral (especially influenza depending on season)
Nosocomial Pneumonia
Gram-negative rods (Enterobacteriaceae, Pseudomonas
aeruginosa), S. aureus, S. pneumoniae, Legionella, anaerobes
Aspiration Pneumonia
Often noninfectious chemical pneumonitis
Develops within 2 hours after event
697
Resolves in 4-5 days

True pneumonia is late development (>2 days after event),
likely superinfection
Anaerobic bacteria are commonBacteroides,
Peptostreptococcus, Fusobacterium
Usual bugs (vary with clinical setting, i.e., community
vs. nosocomial) are also still common (if infectious).
EPIDEMIOLOGY
2,000,000 cases/year
40,000-70,000 deaths/year
Major problem in geriatric population
Most common hospital-acquired infection, complicating
0.3%-0.7% of hospitalizations
Risk factors
Intubation
Age >70 years
Chronic lung disease
Poor nutrition
Risk of aspiration (see below)
Thoracic or upper abdominal surgery
Immunosuppression
Risk factors
Altered consciousnessalcoholism, stroke, dementia,
seizure, drug overdose, head trauma
Dysphagiastroke, neuropathy, myopathy
Recent vomiting or gastroesophageal reflux disease
Nasogastric or endotracheal intubation
Classic presentation (often correlates with typical organisms) includes
Abrupt onset
High fever and chills
Cough productive of purulent sputum
Constitutional symptoms (malaise, fatigue), dyspnea
698
III DISEASES
Symptoms can be very nonspecific, especially among elderly

or hospitalized patients
Nonspecific fever
Mental status change
Nonproductive cough
Pleuritic chest pain
Atypical presentationoften, but not always, correlates
with atypical organism
Often young, otherwise healthy (except for Legionella in
elderly smoker)
Gradual onset and progression
Fever
Constitutional symptoms predominate
Nonproductive cough
Chest X-ray worse than exam
Classic exam findings include
Fever
Abnormal vital signstachycardia, tachypnea, hypoxia
Abnormal lung examcrackles, egophony, bronchial
breath sounds
Complications
Respiratory
No specific management
Consider
Checking arterial blood gas values
Administering oxygen
Administering bronchodilators (albuterol, ipratropium)
via metered dose inhaler or nebulizer
Invasive airway management
Empyema
Purulent pleural effusion
Often polymicrobial, multiple species of both aerobic and
anaerobic bacteria (anaerobes found in up to 75% of cases)
Diagnosis
Thoracentesiscell count, LDH, culture, pH, glucose (in
addition to whatever else you would order)
699
Critical questionDoes it need drainage? The answer is

yes if
pH <7.1 (best single test)
LDH >1,000 U/L
Cell count >25,000/L (>25 109/L)
Glucose <40 mg/dL
Treatment
Drainage (chest tube)
IV antibiotics
Add clindamycin if not already in regimen (metronidazole is probably less effective).
Note that some antibiotics (aminoglycosides and some lactams) may be inactivated in presence of pus and low pH.
Outpatient
Chest X-ray (to make diagnosis)
CBC
Pulse oximetry
Decide whether to admit (see below)
Inpatient
Chest X-ray
LabCBC, electrolytes, ALT, alkaline phosphatase, HIV
if 15-54 years old and high prevalence in community
Blood cultures
SputumGram stain is inexpensive and useful if positive.
Culture is less useful and in modern therapy has little
effect on management.
Tap pleural effusion if present, send for cell count, pH,
LDH, protein, glucose, Gram stain, and culture (acid-fast
bacillus stain optional).
Determine severity of illness and triage according to the
Fine criteria (Table 1).
Evaluation
Blood culture for all patients
Fine criteria not validated on these patientsmay not
apply.
700
III DISEASES
Table 1. Fine Criteria for Triage of Pneumonia
If all of the following are true:
Age <50 years
No history of CHF, cancer, stroke, renal disease, liver disease
Vital signs: pulse <125, respirations <30, temperature <40C
& >35C, SBP >90 mm Hg
Mental status normal
Then triage to outpatient management (Class 1)
Else, check BUN, sodium, glucose and use the following scoring
system:
Score
Age
Age (years)
Female
10
Nursing home resident
10
Active cancer
30
Liver disease
20
CHF, history of stroke, renal disease
10 each
Mental status change, respirations >30, or
20 each
SBP <90 mm Hg
Temp >40C or <35C
15 each
Pulse >125
10
Presence of plural effusion
10
pH <7.35
30
BUN >30 mg/dL or sodium <130 mEq/L
20 each
Glucose >250 mg/dL, hematocrit <30%,
10 each
pO2 <60 mm Hg
CHF, congestive heart failure; SBP, systolic blood pressure.
Consider obtaining sputum sample (deep suction, bronchoscopy, etc.).
Evaluationsame as for community-acquired pneumonia
Infiltrate is most common in superior segment (if patient
was supine) or lower segments (if patient was erect) of right
lower lobe.
MANAGEMENT
Outpatient
Preferred
701
Doxycycline is appropriate if patient is <50 years old and

otherwise healthy.
Erythromycin (most cost-effective), azithromycin, and
clarithromycin are next choices.
Levofloxacin, gatifloxacin, moxifloxacin (not ciprofloxacin)
are extremely effective but expensive, and there is concern
about encouraging resistance.
Alternativeamoxicillin-clavulanate (Augmentin), PO
cephalosporin
Treat 7-10 days (afebrile at least 3 days), except azithromycin
for 5 days total.
Inpatient
Standardfluoroquinolone (levofloxacin, gatifloxacin)
First dose IV
Convert to PO dosing as soon as able.
Alternativethird-generation cephalosporin IV macrolide
(if concern for atypical)
Initiate antibiotics within 4 hours after admission
Treat 10-14 days (afebrile at least 3 days), except azithromycin
for 5 days total.
Nonneutropenic
Cefepime or ceftazidime or piperacillin-tazobactam (Zosyn)
If severely ill, add ciprofloxacin IV (or other antipseudomonal fluoroquinolone) or an aminoglycoside.
If question of aspiration, add clindamycin or metronidazole
(not needed with piperacillin-tazobactam)
Neutropenic
Imipenem-cilastatin or as for nonneutropenic
Add vancomycin if line source is suspected.
If patient is still febrile on day 3, add amphotericin.
Standard regimen (i.e., levofloxacin) + clindamycin or
metronidazole
Clindamycin above the diaphragm, metronidazole below
the diaphragm is quoted but is largely theoretical and
based on scanty clinical evidence.
702
III DISEASES
Clindamycin is probably better in lung abscess.
Alternativepiperacillin-tazobactam or amoxicillin-clavulanate
General Measures for All Types of Pneumonia

Cough
Use combination expectorant (guaifenesin) or antihistamine
(Phenergan) plus suppressant (codeine, dextromethorphan,
benzonatate)such as
Robitussin AC 10 mL every 4 hours
Robitussin DM 10 mL every 6 hours
Phenergan with codeine 5 mL every 4 hours
Tessalon Perles 3 times daily
Fever
Acetaminophen as needed
Hypoxia/Ventilation
Treat hypoxia! Oxygen as needed (saturation >89%)
Chest physiotherapy
Incentive spirometer
Dehydration or Inadequate Oral Intake

IV fluids as needed
Monitoring
Vital signs
Rapid respirations and pulse can indicate decompensation.
Fever should resolve in 48 hours with appropriate therapy.
Pulse oximetry (do not need to follow arterial blood gases for
oxygenation)
Arterial blood gases if acidosis, hypercarbia
No need to monitor chest X-ray unless worsening of clinical
status (takes weeks for infiltrate to resolve)
Initially, watch renal function, electrolytes, CBC daily and
liver function tests if abnormal or every 3-4 days.
Pleural Effusion
Tap all effusions.
703
III DISEASES
POISONINGS AND OVERDOSES
Geeta G. Gyamlani, M.D.
Robert W. Hoel, Pharm. D.
DEFINITIONS
Poisoningharmful effects following exposure to chemicals
Overdosageexposure to excessive amounts of a substance
normally intended for consumption
EPIDEMIOLOGY
In the U.S., chemical exposures result in >5 million requests
for medical advice or treatment annually.
DIAGNOSTIC APPROACH
History
SATS (substance, amount ingested, time ingested, symptom)
Obtain AMPLE (age and allergies, medications, past history of ingestions and past medical history, time of last meal
because it may influence absorption, events leading to present condition) information
Diagnosis of the exact substance involved in overdose or
poisoning should never take precedence over stabilization
of the patient.
In case of self-ingestion, confirm the history by a second
source whenever possible.
In suicide attempts, data provided by patient may be inaccurate or even contrived.
Physical Exam
Vital signs should be recordedheart rate, blood pressure,
temperature, respiratory rate.
Mental status should be categorized.
Eyesnystagmus, pupil size, pupil reactivity
Special abbreviations used in this chapter: CNS, central nervous system; D5W,
5% dextrose in water; GABA, -aminobutyric acid; NAC, N-acetylcysteine.
705
Abdomenbowel sounds, bladder size

Skinburns, bullae, color, warmth, puncture marks
Breathodor
Physical exam findings may help characterize the poisoning as a classic toxidrome, which can be extremely helpful, especially when the ingested agent is unknown (Table 1).
Lab Exam
Will vary depending on individual scenario and clinical suspicions of an astute clinician
The following studies may assist in the evaluation of selected patients:
Arterial blood gasdetects hypercarbia, hypoxemia, and
important acid-base disorders
Anion gapNa+ (HCO3 + Cl) >12 mEq/L
Osmolar gap is the difference between measured and calculated osmolality.
2 Na+ + glucose/18 + BUN/2.8
Osmolar gap >10 mOsm/L suggests presence of an
osmotically active substance (ethanol, methyl alcohol,
ethylene glycol, isopropyl alcohol, or acetone).
Drug screens for urine and plasma are necessary because
many agents first detected in urine are then quantified in
plasma.
Table 1. Classic Toxidromes

Poisoning
Cholinergic
Anticholinergic
Sympathomimetic
Narcotic
Sedative, hypnotic
Symptoms
SLUDGEsalivation, lacrimation,
urination, defecation, gastrointestinal upset,
& emesis
Also bradycardia, confusion, miosis, &
fasciculations
Dry skin, hyperthermia, mydriasis,
tachycardia, delirium, thirst
Hypertension, tachycardia, seizures,
mydriasis, & CNS excitation
Miosis, respiratory depression, & depressed
level of consciousness
Depressed level of consciousness,
respiratory depression, & hyporeflexia

706
III DISEASES
Urine toxicology screens may detect agents not screened

in plasma, including drugs of abuse.
Plasma toxicology screens include drugs, many of which
are tested quantitativelyacetaminophen, salicylates, carboxyhemoglobin, ethanol, methyl alcohol, ethylene glycol, theophylline, phenytoin, lithium, digoxin, barbiturates, and tricyclic antidepressants.
Because of potential necessary alterations in drug extraction lab techniques (based on drug-specific dissociation
constant [pKa, etc.]), the lab should be notified of the clinical suspicions about the type(s) of drug ingested.
MANAGEMENT (GENERAL)
Airway, breathing, and circulation
Patients with depressed level of consciousness should receive
50% dextrose, 50 mL
Thiamine, 100 mg
Naloxone, 2-4 mg IV (especially with miosis and respiratory depression), repeated as necessary
Oxygen
Gastric lavage
Activated charcoal, 1 g/kg through orogastric or nasogastric tube
Enhanced elimination
Multiple doses of activated charcoal, 12.5 g/hour, for drugs
with enterohepatic circulation (barbiturates, phenytoin,
carbamazepine, tricyclic antidepressants, theophylline,
digoxin).
Alkaline diuresis for barbiturate and salicylate toxicity
3 Ampules bicarbonate added to 1 L of 5% dextrose in
water (D5W) IV starting at 2-3 mL/kg per hour adjusted to keep urine pH >7 and urine flow of 2-3 mL/kg per
hour
Acidification of urine is controversial for ingestions involving amphetamines, quinine, and phencyclidine because
risks outweigh benefits.
Hemodialysis
Useful in elimination of water-soluble, low-molecular
707
weight toxins (alcohols, amphetamines, phenobarbital,

lithium, salicylates, theophylline, thiocyanate)
Is most effective in removing drugs with low protein
binding and low volume of distribution (VD)
- VD = (amount drug ingested/plasma concentration)
1/weight
SPECIFIC INTOXICATIONS
Acetaminophen
Second leading cause of toxic prescription drug ingestion
in the U.S.
Toxic Mechanism
95% of acetaminophen metabolism involves formation of
sulfate and glucuronide conjugates that are then excreted by
the kidney.
5% of the metabolism involves oxidation by cytochrome
P450-dependent enzymes to N-acetyl-p-benzoquinoneimine
(NAPQI), a toxic metabolite normally removed by conjugation with glutathione.
Large doses of acetaminophen prompt increased use of the
glutathione pathway, leading to depletion of glutathione and
accumulation of the toxic metabolite.
Predisposing conditions leading to toxicity are
Depletion of glutathione (chronic alcohol ingestion, malnutrition, HIV infection)
Drugs that enhance P450 microsomal enzymes (barbiturates, phenytoin, rifampin)
Clinical Features
Nausea (first 24 hours)
Evidence of liver toxicityelevated aminotransferase levels,
right upper quadrant tenderness (from 24 to 72 hours)
Evidence of progressive hepatic injury and fulminant hepatic failureencephalopathy, coagulopathy (after 72 hours)
Diagnosis
The Rumack-Matthew nomogram is designed to determine
potential acute hepatotoxicity and need for N-acetylcystein
(NAC) treatment.
A serum acetaminophen level above the lowest line on the
708
III DISEASES
Rumack-Matthew nomogram between 4 and 24 hours after

ingestion indicates possible hepatotoxicity and need for antidote therapy (Fig. 1).
Ingestion of 150 mg/kg or more may be associated with
acute hepatotoxicity; if 7.5 g or more is ingested, serum level
should be measured.
Treatment
Gastric lavage
Activated charcoal
Interferes only slightly with NAC absorption
No dose adjustment needed for NAC
NAC is a glutathione analogue that helps inactivate the toxic
acetaminophen metabolite.
4000
Plasma acetaminophen concentration
3000
500
Lower limit for high-risk group

Lower limit for probable-risk group
Study nomogram line
400
2000
300
1300
200
1000
150
100
500
50
100
10
50
30
mmol/L mg/mL
12
16
20
24
28
Hours after acetaminophen ingestion
Fig. 1. Nomogram to define risk according to plasma concentration

of acetaminophen. (Modified from Rumack BH, Matthew H.
Acetaminophen poisoning and toxicity. Pediatrics. 1975;55:871-6.
709
NAC is most effective if started within 8-24 hours after acetaminophen overdose.
It is reasonable to administer NAC if level of acetaminophen
is toxic after 24 hours or possible liver injury is detectable.
Recommended PO dose of NAC140 mg/kg loading dose,
followed by 70 mg/kg every 4 hours for 17 doses
Dilute 10% or 20% NAC to 5% in juice, soft drink, or
water to give PO or by nasogastric tube
Adverse reactions to NAC include nausea, vomiting, and
diarrhea.
Ethanol
Ethanol is the most frequent agent of intoxication, characterized by clinical effects of acute or chronic exposure.
Coingestion with sedatives, tranquilizers, stimulants, or other
agents is common and greatly increases likely toxicities of
the agents involved.
Ethanol is present in many household products as well as in
beverages.
Toxic Mechanism
Ethanol is a central nervous system (CNS) depressant.
Ethanol is hepatotoxic because of NADH production in its
alcohol dehydrogenase pathway. Hepatic lipid accumulation results in fatty liver.
Clinical Features of Acute Exposure

Dose-related CNS depression ranging from mild inebriation
to ataxia, narcosis, coma, respiratory failure, loss of airway
protection, and death
Hypothermia
Hypoglycemia with possible seizures
Lactic acidosis or ketoacidosis
Electrolyte imbalance
Gastrointestinal upset with possible bleeding
Clinical Features of Chronic Exposure

Neurologic changes from amnesia to dementia and somnolence
Cardiac myopathy
Hepatotoxicity with potential irreversible necrosis and
cirrhosis
710
III DISEASES
Gastrointestinal tract bleeding, including esophageal varices

Pancreatitis
Malnutrition predisposing to hypoglycemia, ketoacidosis,
and osmolar gap
Fetal alcohol syndrome
Physical dependence with characteristic withdrawal syndrome can persist for several days.
It is characterized by agitation, shaking, sweating, hyperreflexia, tachycardia, and possible seizures.
Delirium tremens, occurring in about 5% of patients, is syndrome of profound confusion, hallucinations, and gross
tremor; it can be fatal.
Diagnosis
Ethanol level in blood, serum, plasma, and breath
Serum level >0.4% (400 mg/dL) is considered severe
intoxication.
Blood glucosehypoglycemia delayed up to 6 hours after
ingestion
Transaminase and INR elevationmay expose hepatotoxicity
CK, BUN/creatininemay reveal rhabdomyolysis effects
Increased anion and osmolar gaps
Treatment of Acute Exposure

Maintain a safe airway; intubate if necessary.
Gastric lavage
Activated charcoal if other substances are potentially ingested (does not absorb alcohols)
50% dextrose if indicated
Dextrose IV infusion preceded by 100 mg thiamine to prevent Wernicke encephalopathy
Lorazepam if seizuresadults, 2-4 mg IV; children, 0.05-0.1
mg/kg
Hemodialysis in severe toxicity
Treatment of Chronic Toxicity

Thiamine, 100 mg IV or IM, always to be given before IV
glucose bolus
711
Folic acid supplementation

Lorazepam IV for seizures
Lorazepam PO or IV for ethanol withdrawal syndrome
Ethylene Glycol
Ethylene glycol is used as a solvent for plastics, paints, windshield cleaners, antifreeze, and deicer preparations.
Toxic Mechanism
Ethylene glycol is oxidized by alcohol dehydrogenase to glycolic acid, glycoxylic acid, and oxalic acid, which cause CNS
depression and interstitial and tubular damage to the kidney.
Clinical Features
Nausea, vomiting, and abdominal pain
Sweet aromatic odor to breath
Slurred speech, ataxia, nystagmus, seizures, and coma
Hypotension
Pulmonary edema
Oliguria, anuria, and acute renal failure
Diagnosis
Serum ethylene glycol and glycolic acid levels
Oxalate crystals in urine
Most commercial antifreeze preparations contain fluorescein, which causes urine to fluoresce under Wood lamp examination, thereby fostering a rapid presumptive diagnosis in the
appropriate setting, pending confirmation by other studies.
Treatment
Maintain a safe airway; intubate if necessary.
Gastric lavage
Activated charcoal if other substances are potentially ingested (does not absorb alcohols)
50% dextrose if indicated
Thiamine, folic acid, and pyridoxine supplement
Because alcohol dehydrogenase has a higher affinity for
ethanol than for ethylene glycol or methanol, ethanol is
administered orally or 5% or 10% ethanol in D5W IV to
maintain ethanol blood level at 100-150 mg/dL.
712
III DISEASES
Fomepizole (methylpyrazole) inhibits the alcohol dehydrogenase enzyme, thereby slowing the metabolism of ethylene
glycol or methanol.
Hemodialysis for visual impairment (methyl alcohol), renal
failure, pulmonary edema, significant or refractory acidosis, and ethylene glycol (or methyl alcohol) level >25 mg/dL
Methyl Alcohol
Component of varnishes, paint removers, and windshield
washer solutions and a denaturant that makes ethanol unfit
for consumption
Toxic Mechanism
Methyl alcohol is metabolized to formaldehyde and formic
acid by alcohol dehydrogenase which injure the retina.
Clinical Features
Nausea, vomiting, and abdominal pain
Sweet aromatic odor to breath
Slurred speech, ataxia, nystagmus, seizures, and coma
Hypotension and bradycardia
Ophthalmologicclouding and diminished vision, flashing
spots, dilated or fixed pupils, hyperemia of optic disc, retinal edema, and blindness
Diagnosis
Serum levels of methyl alcohol
Treatment
Same as for ethylene glycol poisoning
Benzodiazepines
Most commonly overdosed prescription drugs in the U.S.
Toxic Mechanism
Potentiation of the inhibitory effects of -aminobutyric acid
(GABA) on CNS by binding to the GABA receptors and
713
increasing frequency of opening of chloride channels in

response to GABA stimulation
Clinical Features
Dose-dependent depression in level of consciousness not
usually accompanied by respiratory or cardiovascular
depression
Airway protection, including intubation, may be necessary.
Diagnosis
History
Urine metabolites may be helpful, although a negative result
does not exclude the diagnosis.
Treatment
A benzodiazepine receptor antagonist (flumazenil) is available as a diagnostic and therapeutic tool.
Flumazenil0.2 mg over 15 seconds and 0.2 mg every
minute up to a cumulative dose of 1 mg, titrated to effect
Doses from 3 to 10 mg have been necessary in some
cases.
Flumazenil reverses the sedative effects of benzodiazepines
but is inconsistent in reversing the respiratory depression
and should not be used as a substitute for intubation in patients
with notable respiratory depression.
Because of the risk of seizures, flumazenil is contraindicated for patients with mixed overdoses involving tricyclic antidepressants and patients physically dependent on benzodiazepines.
Resedation is likely because of the short half-life of flumazenil compared with that of benzodiazepines.
Digoxin
Of patients receiving digoxin, 25% develop toxic reactions,
but most are nonlife-threatening.
Toxic Mechanism
Cardiac glycosides act by inhibiting sodium-potassium
ATPase, leading to increased intracellular levels of sodium
and calcium and a corresponding efflux of potassium, resulting in decreased intracellular potassium levels.
714
III DISEASES
Clinical Features
Nausea, vomiting, abdominal pain, and diarrhea
Confusion, delirium, and hallucinations
Blurred vision, xanthopsia (yellow vision), photophobia,
and scotomata
Premature ventricular contractions (most common), sinus
arrhythmia, sinus bradycardia, all degrees of atrioventricular block, bigeminy, ventricular tachycardia, and ventricular
fibrillation
Acute toxicity is often exhibited by hyperkalemia, and in
chronic toxicity, hypokalemia can be a predisposing feature.
The combination of supraventricular tachyarrhythmia and
atrioventricular block is highly suggestive of digitalis toxicity.
Diagnosis
Increased serum levels of digoxin (3-5 ng/mL in chronic
toxicity; very high levels, 50-60 ng/mL, usually seen with
acute overdose)
Treatment
Repeated activated charcoal doses to enhance elimination
Hemodialysis, hemoperfusion, and diuresis are ineffective.
Patients with normal renal function clear ~30% of the
total body amount and anuric patients, ~14%.
Correct potassium, magnesium, and calcium abnormalities.
Treat ventricular tachyarrhythmias with magnesium sulfate,
phenytoin, or lidocaine.
Immunotherapy with digoxin-specific Fab-fragment antibodies used for patients with potentially life-threatening toxicity not responsive to the above measures
Dose of Fab-fragment antibodies is calculated by estimating total body content of digoxin.
Each 40 mg (1 vial) of Fab-fragment antibodies binds to
0.6 mg of digoxin.
Usually 1-2 vials are sufficient for chronic digoxin toxicity, but 15-20 vials may be required for acute overdose.
Although free digoxin levels decrease rapidly to zero after
antibody administration, routine methods used to measure
715
digoxin levels do not distinguish between bound and

unbound drug; hence, drug levels do not correlate with
toxicity after antibody therapy.
May cause sensitization (to future doses) after administration
Expensive
Salicylates
Found in many over-the-counter drugs such as aspirin, bismuth salicylate (Pepto-Bismol), and oil of wintergreen.
Toxic Effects
Increases sensitivity of the respiratory center to changes in
PaO2 and PCO2, with an increase in rate and depth of respiration causing respiratory alkalosis
Later causes uncoupling of oxidative phosphorylation and
metabolic acidosis
Clinical Features
Tinnitus, vomiting, diaphoresis, and hyperventilation
Respiratory depression, convulsions, and coma
Hepatotoxicity with prolonged PT
Noncardiogenic pulmonary edema
Cardiovascular collapse
Diagnosis
Positive ferric chloride test in urine
Serum salicylate levels
Mild <40 mg/dL
Moderate 40-100 mg/dL
Severe >100 mg/dL
Anion gap metabolic acidosis
Treatment
Gastric lavage
Activated charcoal
Alkalization of urine to enhance elimination of salicylate if
salicylate level >35 mg/dL
Hemodialysis is indicated for salicylate levels >100 mg/dL,
refractory seizures, alteration in mental status, or refractory
acidosis.
716
III DISEASES
Tricyclic Antidepressants
Leading cause of death from pharmaceutical drug overdose
in the U.S.
Toxic Mechanism
Toxicity results from
Anticholinergic actions
Block of the reuptake of neurotransmitters such as
norepinephrine
Clinical Features
Pupillary dilatation, delirium, seizures, and coma
Tachycardia, hypertension, hypotension, prolonged QRS
interval (>0.10 second), and arrhythmias (ectopic beats) and
wide complex tachycardia
Diagnosis
Serum levels confirm ingestion but do not correlate well
with clinical toxicity.
Prolongation of QRS interval can be a prognostic sign of
progression to seizures (QRS >0.10 second) and serious
arrhythmias (QRS >0.16 second)
Treatment
Maintain a secure airway.
Stabilize vital signs.
ECG monitoring
Gastric lavage
Activated charcoal
Magnesium sulfate for torsades de pointes
Benzodiazepines for seizures
Norepinephrine or phenylephrine for refractory hypotension
Alkalization of blood with sodium bicarbonate to a pH of
7.45-7.55 for prolonged QRS or wide complex tachycardia
Bicarbonate is also useful for refractory seizures and
hypotension.
717
III DISEASES
PULMONARY THROMBOEMBOLISM
Ives R. De Chazal, M.D.
DEFINITION
Embolization of a thrombus (usually formed in deep veins of
lower extremities, pelvis, or upper extremities) to pulmonary
vasculature
CLASSIFICATION
The clinical presentation may be classified as symptomatic,
asymptomatic, or massive.
ETIOLOGY
Pulmonary embolism (PE) most commonly results from
deep venous thrombosis (DVT) of proximal deep veins of the
lower extremities, including the popliteal veins.
Hypercoagulability leading to the development of thrombosis occurs in patients with risk factors (Table 1):
Venous stasis, as with immobilization
Endothelial injury, as in surgery
Coagulopathy
Other risk factors include oral contraceptives or postmenopausal estrogen, pregnancy, and inherited or acquired
hypercoagulable disorders (e.g., factor V Leiden).
EPIDEMIOLOGY
Annually in the U.S., 250,000-300,000 patients are hospitalized with diagnosis of PE.
One-year mortality of up to 25% can be decreased to 2%-8%
with treatment.
Incidence doubles with each decade of life.
Special abbreviations used in this chapter: ABG, arterial blood gas; DVT, deep
venous thrombosis; PE, pulmonary embolism; VTE, venous thromboembolism.
719
Table 1. Hypercoagulable States

Inherited
Factor V Leiden mutation
Antithrombin III deficiency
Protein C deficiency
Protein S deficiency
Prothrombin 20210A
Dysfibrinogenemia
Impaired clot lysis
Acquired
Disseminated intravascular coagulopathy
Lupus anticoagulant
Antiphospholipid antibody syndrome
Myeloproliferative disorders
Heparin-induced thrombocytopenia
Hyperviscosity syndromes (e.g., Waldenstrm macroglobulinemia)
Malignancy
Data from Mateo J, Oliver A, Borrell M, Sala N, Fontcuberta J. Laboratory
evaluation and clinical characteristics of 2,132 consecutive unselected patients
with venous thromboembolism: results of the Spanish Multicentric Study on
Thrombophilia (EMET-Study). Thromb Haemost. 1997;77:444-51.
Estimate: clinically unsuspected PE occurs in 30%-50% of

patients with DVT.
In postoperative patients, asymptomatic PE occurs 4 times as
often as symptomatic PE, thus the paramount importance of
venous thromboembolism (VTE) prophylaxis.
In up to 70% of patients who die of PE, diagnosis is not
suspected before death; thus, a high index of suspicion must
be maintained.
Signs and symptoms are common but typically nonspecific.
Most common presentation in symptomatic patients is unexplained dyspnea with or without chest pain.
Symptomsdyspnea (73% of patients), pleuritic chest pain
(66%), cough (37%), and hemoptysis (13%)
Signstachypnea (70% of patients), rales (51%), and tachycardia (30%)
720
III DISEASES
DIAGNOSTIC STRATEGY
Clinical approach to diagnosis of acute PE varies depending on
Patient factors (e.g., underlying lung disease)
Local institution-specific diagnostic and therapeutic capabilities
Hemodynamic status
First, establish the degree of clinical suspicion (low, intermediate, or high) based on the risk factors, history, and physical exam and by excluding other conditions.
Initial evaluation includes chest X-ray, arterial blood gases
(ABGs), and ECG.
ABGsPatients with PE commonly have hypoxemia,
hypocapnia, and thus increased alveolar-arterial gradient.
Although ABG findings are helpful in the evaluation, PE
cannot be diagnosed based on these findings only because
many conditions that mimic PE manifest with hypoxemia.
In PIOPED study, 8% of patients with PE had normal
alveolar-arterial gradients.
ECGimportant for ruling out acute coronary syndrome
and pericarditis.
Most common ECG finding is sinus tachycardia.
Classic S wave in lead I and Q and T waves in lead III
findings and other signs of acute cor pulmonale (new right
bundle branch block, P pulmonale, and right axis deviation)
occur in <30% of patients with PE.
Chest X-rayNormal findings in setting of severe dyspnea
and hypoxemia of acute onset strongly suggest PE.
Abnormal findings are common but nonspecific.
Classic findings such as focal oligemia (Westermark sign)
and peripheral wedge-shaped density (Hampton hump)
are suggestive but infrequent.
Ventilation/perfusion (V/Q) lung scanmost useful initial
evaluation tool, particularly in patients without preexistent
lung disease
V/Q scan results are traditionally reported as normal, low
probability, intermediate probability, and high probability.
Normal perfusion study result practically excludes PE,
but a high-probability result warrants therapy.
721
Combining the data of the degree of clinical suspicion

and the results of the V/Q scan add to the accuracy of the
evaluation (Table 2).
Venous ultrasonographyhighly accurate study in patients
with suspected DVT
A negative study cannot rule out PE.
Approximately 30% of patients with PE by pulmonary
angiography have normal lower extremity ultrasound findings.
Positive lower extremity ultrasound findings require therapy.
Pulmonary artery angiographygold standard for diagnosis of PE
Useful when clinical suspicion is low and other tests indicate PE
Also helpful in cases of high clinical suspicion of PE and
nondiagnostic V/Q scan (and/or a negative ultrasound
study of the extremities)
Complication rates have declinedmortality, 0.5%; major
complications, 1%; minor complications, 5%
Other important diagnostic studies
D-dimer
A fibrin degradation product that indicates activation
of the coagulation pathway
High in PE and DVT but also trauma, metastatic cancer,
postoperative state, sepsis, late pregnancy, and advanced
age
When increased, its specificity ranges from 30% to
70%.
A negative ELISA study virtually rules out PE, with a
negative predictive value of 99%.
Table 2. Likelihood of Pulmonary Embolism in Settings

of Various Index of Suspicion and
Ventilation-Perfusion (V/Q) Scan Results
V/Q scan
results
Normal
Probability
Low
Intermediate
High
722
Low
Clinical index of suspicion

Intermediate
High
<2%
6%
<2%
4%
16%
56%
16%
28%
88%
40%
66%
96%
III DISEASES
ELISA is preferable to latex method.

Spiral CT
Best for identifying PE in proximal pulmonary vasculature, may not identify distal emboli
With 70% sensitivity and 91% specificity, a negative
study does not conclusively rule out PE.
Allows study of lung parenchyma, possibly clarifying
an alternative diagnosis
Has obviated the need for pulmonary artery angiography in many cases
MRI
Preliminary studies suggest sensitivity of 75%-100%
and specificity of 95%-100%.
May have the advantage in diagnosing DVT and PE at
the same time and avoiding nephrotoxic contrast agents
Echocardiography
Role in diagnosis of PE is undefined
May yield important information (i.e., with regard to
right-sided heart strain) when evaluating acute hemodynamic compromise in patient with suspected massive
PE
MANAGEMENT
Start heparin promptly if clinical suspicion is moderate to
high, in the absence of contraindications (e.g., gastrointestinal tract bleed), until definitive evaluation is complete.
Warfarin should always be instituted within the course of
heparinization.
Unfractionated Heparin
Bolus of 80 U/kg and continuous infusion of 18 U/kg per
hour
aPTT goal1.5-2 times normal value
Adjustments are made according to aPTT results 4-6 hours
later (Table 3).
Complicationsmajor bleeding, 2%-3% of patients; heparininduced thrombocytopenia, 2.7%, with subsequent risk of
thrombosis and osteoporosis
723
Table 3. Weight-Based Nomogram for Heparin Dosing

Initial dose
aPTT <35 seconds (<1.2
control)
aPTT, 35-45 seconds
(1.2-1.5 control)
aPTT, 46-70 seconds
(1.5-2.3 control)
aPTT, 71-90 seconds
(2.3-3 control)
aPTT >90 seconds (>3
control)
80 U/kg bolus, then 18 U/kg

per hour
per hour
per hour
No change
Decrease infusion rate by 2
U/kg per hour
Hold infusion 1 hour, then
decrease infusion rate by 3
U/kg per hour
From Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The
weight-based heparin dosing nomogram compared with a standard care
nomogram: a randomized controlled trial. Ann Intern Med. 1993;119:87481. Used with permission.
Low-Molecular-Weight Heparin
May be as effective as unfractionated heparin in treating
VTE with comparable major bleeding profile
Advantagesconventional dosing and administration, no
need to follow aPTT, thus facilitating outpatient treatment and
potential for cost savings
Heparin-induced thrombocytopenia can occur
Disadvantageshigher drug cost and incomplete reversal
by protamine
Contraindicated in renal failure with creatinine clearance
<30 mL/hour
Enoxaparin sodium dose is 1 mg/kg SQ every 12 hours or 1.5
mg/kg SQ daily (not to exceed 180 mg daily).
Warfarin
Warfarin can reduce protein C levels faster than factors II, IX,
and X, creating a relative and transient (4 days) hypercoagulable state; thus, heparin is always started first.
Heparin and warfarin should overlap until INR is 2.5-3 for
2-3 days.
Load with warfarin 5 mg unless the patient weighs >85 kg,
then use 7.5 mg.
724
III DISEASES
Duration of therapy
First event with time-limited risk factors3-6 months
Idiopathic VTE6 months
May treat with subtherapeutic warfarin (INR 1.5-2) lifelong after check.
History of cancer, anticardiolipin antibodies, antithrombin
deficiency, recurrent PE or thrombophilia12 months to
life
Thrombolytic Therapy
Indicated for patients with massive PE and hypotension
May improve pulmonary artery perfusion in 2 hours and be
lifesaving
Central administration offers no outcome advantage.
If thrombolysis is contraindicated, catheter and/or surgical
embolectomy may be considered.
Incidence of intracerebral hemorrhage is 2%.
Contraindicated in active bleeding and cerebral metastasis
Inferior Vena Cava Filters

The two best filters are the Greenfield and Birds Nest
Indicated in VTE when anticoagulation is contraindicated,
VTE is recurrent despite anticoagulation, and when underlying cardiopulmonary status is so severe that recurrent PE
may be fatal
Filters do not halt DVT, and the incidence of DVTs distal
to the filter may increase.
Filters and anticoagulation do not decrease 2-year mortality compared with anticoagulation alone.
DVT Prophylaxis
Approximately 2/3 of patients do not receive prophylaxis
despite clear indications (Table 4).
Incidence of DVT and fatal PE in orthopedic surgery patients
(without prophylaxis) is reportedly as high as 30% and 14%,
respectively.
PE is the most common and preventable cause of hospital
death.
725
Table 4. Examples of Level of Deep Venous Thrombosis

Risk
Level of risk
Lowminor surgery in patients <40
years with no additional risk factors
Moderateminor surgery in patients
with additional risk factors, nonmajor surgery in patients 40-60
years with no additional risk
factors, major surgery in patients
<40 years with no additional risk
HighNonmajor surgery in patients
>60 years or with additional risk
factors, major surgery in patients
>40 years or with additional risk
factors
Highestmajor surgery in patients
>40 years plus prior VTE, cancer,
or molecular hypercoagulable state;
hip or knee arthroplasty, hip
fracture surgery; major trauma;
spinal cord injury
Successful prevention
strategies
No specific measures
Aggressive mobilization
LDUH* every 12 hours,
LMWH, ES, or IPC
LDUH every 8 hours,

LMWH, or IPC
LMWH, oral anticoagulants, IPC/ES plus

LDUH*/LMWH, or ADH
ES, elastic stockings; IPC, intermittent pneumatic compression; LDUH, lowdose unfractionated heparin; LMWH, low-molecular-weight heparin; VTE,
venous thromboembolism.
*5,000 U SQ.
For example, enoxaparin 30 mg SQ twice daily (orthopedic surgery) or 40
mg SQ daily (general surgery); dalteparin 2,500-5,000 anti-Xa units SQ
daily.
726
III DISEASES
SEPSIS
Axel Pflueger, M.D.
Timothy R. Aksamit, M.D.
DEFINITIONS AND CLASSIFICATION

Standardization of terminology according to the 1992
American College of Chest Physicians/Society of Critical
Care Medicine Consensus
Infectioninflammatory response to microorganisms
Bacteremiapresence of viable bacteria in blood
Systemic inflammatory response syndrome (SIRS)
inflammatory response to various insults
Is defined by 2 of the following:
Temperature >38C or <36C
Heart rate >90 beats/min
Respiratory rate >20 beats/min or PaCO2 <32 mm Hg
WBC >10,000/mm3 (>10 109/L) or <4,000/mm3
(>4 109/L), >10% immature band forms
Sepsisinfection plus SIRS
Multiorgan dysfunction syndromeinflammatory-mediated injury involving several organ systems in an acutely
ill patient such that homeostasis cannot be maintained
without intervention
Severe sepsissepsis plus multiorgan system dysfunction
Septic shocksevere sepsis plus hypotension refractory
to fluids (systolic blood pressure <90 mm Hg or a decrease
of 40 mm Hg from baseline in absence of other causes of
hypotension plus hypoperfusion abnormalities, e.g., oliguria, lactic acidosis, acute change in mental status)
EPIDEMIOLOGY
Incidence/prevalence in U.S.176/100,000 persons/year
In U.S., at least 750,000 cases/year, and 225,000 are fatal.
Special abbreviations used in this chapter: ARDS, adult respiratory distress syndrome; SIRS, systemic inflammatory response syndrome.
727
Mortality30%-50%
Ages affectedall
Sex ratiomale = female
Annual incidence increased 9% between 1979 and 2000
Increased incidence contributions from aging population,
increase and prevalence of immunocompromised patients, and
more invasive support of critically ill patients
ETIOLOGY
Microorganisms
Positive blood culturesonly in 30% of cases
The predominant pathogens are listed below:
Gram-positive organisms in 25% of cases (most common)
Staphylococcus aureus in 14% of cases, including methicillin-resistant and methicillin-sensitive S. aureus
Staphylococcus sp in 6%
Streptococcus pneumoniae in 11%
Streptococcus sp in 9%
Enterococcus sp in 7%, including vancomycin-resistant
and vancomycin-sensitive Enterococcus
Others in 4%
Gram-negative organisms in 17% of cases
E. coli in 17%
Klebsiella sp in 7%
Pseudomonas sp in 6%
Enterobacter sp in 5%
Haemophilus influenzae in 4%
Bacteroides sp in 3%
Others in 10%
Mixed organisms in 15% of cases
Fungi in 10% of cases
Candida albicans in 2%
Other Candida sp in 5%
Yeast in 1%
Other fungi, including Pneumocystis carinii (P. jiroveci), in 1%
Anaerobes
Viral diseaseinfluenza, dengue, other hemorrhagic
viruses, coxsackievirus B
Rickettsial diseaseRocky Mountain spotted fever,
endemic typhus
728
III DISEASES
Spirochetal diseaseleptospirosis, relapsing fever

(Borrellia sp), Jarisch-Herxheimer reaction in syphilis
Protozoal diseaseToxoplasma gondii, Trypanosoma
cruzi, Plasmodium falciparum
Common Sources of Sepsis

Lungs in 40%-50% of cases
Bloodstream infections in 10%-30%
Urinary tract in 10%-20%
Intra-abdominal focus (biliary tree, abscess, peritonitis) in
10%-20%
Soft tissue (e.g., in skin, cellulitis, decubitus ulcer, gangrene)
in 1%-5%
Other sites in 1%-5%
Unknown source in 14%-20%
Nosocomial Sepsis
Organisms responsible for nosocomial sepsis and their source
Nosocomial infection and sepsis are especially common in
the ICU.
Table 1. Organisms Causing Nosocomial Sepsis and the

Corresponding Sources
Organism
Source
Gram-negative enteric pathogens

Coagulase-negative staphylococci
Staphylococcus aureus
Pneumonia, urinary tract

Bloodstream infection
Pneumonia, bloodstream
infection
Urinary tract, bloodstream
infection
Pneumonia
Pneumonia, intra-abdominal,
head and neck infection
Urinary tract, bloodstream
infection, intra-abdominal
Enterococci
Streptococci
Anaerobic organisms
Candida sp
729
Pulmonary, bloodstream, and urinary tract are most common sites of ICU nosocomial infection.
Signs and symptoms of sepsis are listed in Table 2.
Differential Diagnosis of SIRS
The differential diagnosis for SIRS is listed in Table 3.
Lab Findings
Positive blood cultures
Positive Gram stain or cultures from other sites (sputum,
urine, CSF, abscess, ascites, pleural fluid, synovial fluid,
bronchoalveolar lavage)
Previous or concurrent antibiotic use may decrease Gram
stain and culture sensitivity.
Blood work abnormalities (hematologic, metabolic, and
organ-specific) are listed in Table 4.
Previous antibiotic use
Pathophysiology
Clinical course driven by host factors (e.g., genetics, comorbidities, and indwelling devices) as well as organism factors (e.g., virulence and size of inoculum)
Table 2. Signs and Symptoms of Sepsis

Generalchills, rigors, diaphoresis, myalgias
Fever (>38C) or hypothermia (<36C)
Respiratorytachypnea, cough, sputum production, dyspnea, chest
pain, cyanosis
Cardiovasculartachycardia, hypotension, rales, gallops, murmur
Renaloliguria, anuria, dysuria, urgency, flank pain
Central nervous systemstiff neck, headache, photophobia, focal
neurologic deficits, mental status changes (restlessness, agitation,
confusion, delirium, lethargy, stupor, coma)
Gastrointestinalnausea, vomiting, diarrhea, abdominal pain,
jaundice
Skin lesionserythema, petechiae, ecthyma gangrenosum, embolic
lesions, purpura fulminans, livedo reticularis
Hematologicbleeding, petechiae, ecchymosis
730
III DISEASES
Table 3. Differential Diagnosis for Noninfectious Causes
of Systemic Inflammatory Response Syndrome
Pancreatitis
Gastric aspiration
Trauma and tissue injury including burns
Blood product support, transfusions
Hemorrhagic shock
Collagen vascular diseases and associated organ injury
Intestinal endotoxin translocation
Drug therapy
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Endocrinethyrotoxicosis, adrenal insufficiency
Cardiovascularvasculitides, dissecting aortic aneurysm, myocardial infarction (rare)
Anaphylaxis (rare)
Table 4. Hematologic, Metabolic, and Organ-Specific

Blood Abnormalities
Leukocytosis or leukopenia
Lactic acidosis
Thrombocytopenia
Prolonged PT/INR
Hypofibrinogenemia
Increased soluble fibrin
monomers
Hyperglycemia or hypoglycemia
Proteinuria
Hypoxemia
Hyperbilirubinemia
Hypercalcemia
Hypoferremia
Complex cascade of inflammatory and anti-inflammatory

mediators (e.g., cytokines), homeostatic factors (e.g., tissue
factor, protein C, protein S, and plasminogen activation),
and other extracellular mediators (e.g., nitric oxide, platelet
activating factor, complement)
Systemic inflammatory, epithelial, and local tissue factors
are all important and interdependent
Pathology Findings
Inflammation at primary site of infection and organ dysfunction
731

Noncardiogenic pulmonary edema and diffuse alveolar damage
TEST ORDERING
Blood culturespositive in only 30% of patients
Serum lactate
Antigen detection systemscounterimmunoelectrophoresis and latex agglutination tests (pneumococcus, H. influenzae type B, group B streptococcus, meningococcus, legionella, histoplasmosis) for select specimens (e.g., urine, CSF)
Polymerase chain reaction on select specimens for select
organisms
Gram stain of buffy coat smears is useful in a very limited
number of cases.
Radiographic studies (e.g., chest X-ray, kidney-ureters-bladder, chest CT, abdominal CT)
Ultrasound, CT, or MRI may be useful in delineating sites of
infection.
Intra-abdominal, pleural, bone, joint, endovascular, and
paranasal sinus infections can easily be overlooked.
Aspiration of potentially infected body fluids (pleural, peritoneal, CSF, synovial)
Hematologic, metabolic, and organ-specific blood tests
(Table 4)
Assessment of oxygenation (e.g., oximetry, arterial blood
gas analysis, and mixed venous oximetry or blood gas analysis)
When appropriate, biopsy and/or drainage of potentially
infected tissues for diagnosis and source control (e.g., abscess,
biliary tree) may be neccessary.
MANAGEMENT
General Measures
Early and appropriate
Resuscitation
Antibiotics
Source control
Time is important
Clinical approach should be proportionate in time (urgency)
and intensity to severity of presenting illness.
Hospitalization for severe sepsis
732
III DISEASES
ICU admission for patients with shock, respiratory failure, or

progressive multiorgan system dysfunction
Review, clarify, and articulate treatment goals and resuscitative status of patient if not already documented.
Organ Failure
Average risk of death increases by 15%-20% with failure of
each additional organ.
Shockoccurs early and resolves rapidly or is fatal
Oliguriaoccurs early and is followed by variable course,
with some patients recovering early and some requiring
dialysis
Central nervous system and liver dysfunctionoccurs hours
to days after onset of sepsis and persists for intermediate
periods
Acute respiratory distressoccurs early and may persist
Initial Resuscitation and Management (Urgent: First 6

Hours)
Within first hour (0-1 hour)
Obtain cultures (e.g., blood, urine, sputum, other).
Begin appropriate antibiotics with one or more drugs
against likely bacterial or fungal pathogens with tailoring to community and health care-associated sensitivity
profiles.
IV access with consideration of placement of central
venous access
Fluid resuscitation started with boluses of crystalloid (2501,000 mL, or 20 mL/kg) every 15-30 minutes, with repeat
boluses pending clinical assessment and response.
Crystalloid: 0.9 normal saline or lactated Ringer solution (albumin and colloid not shown to be of clear benefit)
Within first 6 hours (0-6 hours)
Fluid resuscitation continued and guided to end point of
Central venous pressure of 8-12 mm Hg
Mean arterial blood pressure 65 mm Hg
Urine output 0.5 mL/kg per hour and/or mixed venous
oxygen saturation of 70%
733
Vasopressors started for mean arterial pressure <65 mm Hg

or hypoperfusion (e.g., dopamine or norepinephrine, then
with consideration of vasopressin, phenylephrine, or epinephrine)
Renal dose of dopamine has not been shown to be of benefit and is not recommended.
Transfusion of packed RBCs to be considered if:
Central venous pressure is 8 mm Hg
Mean arterial pressure is >65 mm Hg
Mixed venous oxygenation is <70%, and
Hematocrit is <30%
Inotropic support (e.g., dobutamine) if :
Central venous pressure is >8 mm Hg
Mean arterial pressure is 65 mm Hg
Hematocrit is >30% and
Mixed venous oxygenation is still <70%
Consider bedside transthoracic echocardiography if refractory shock or lack of response is noted.
May need to consider placing pulmonary artery catheter
in setting of persistent shock
Source control with drainage and surgery consultation if
necessary
Continuation Phase and Support (<24 Hours After

Diagnosis of Sepsis)
Within first 24 hours
If hemodynamically unstable (pressor dependent), cosyntropin stimulation test and start of stress dose of corticosteroids, e.g., glucocorticoid (hydrocortisone 50-100 mg
every 6-8 hours) and mineralocorticoid (fludrocortisone,
50 g every day), pending test results (for relative adrenal
insufficiency)
Continue stress dose of corticosteroids for 7 days if increase
in serum cortisol is <9 g/dL after cosyntropin stimulation
test.
Consider infusion of activated protein C for severe sepsis
or septic shock with dysfunction of two or more organ
systems and no contraindications (refer to activated protein
C order set).
Begin ventilatory support for respiratory failure with
endotracheal intubation and low tidal volume protective
734
III DISEASES
strategy for those at risk for or in the presence of acute

lung injury or adult respiratory distress syndrome
(ARDS).
A limited trial of noninvasive positive pressure ventilation may be appropriate if a short duration of ventilatory
assistance is expected.
Elevate head of bed >30 for patients requiring mechanical ventilation as tolerated.
Tight glucose control with avoidance of hyperglycemia;
goal blood sugar of 80-110 mg/dL with use of insulin
infusion (refer to ICU insulin infusion protocol)
Nothing PO
Begin deep venous thrombosis stress prophylaxis with
specific treatment proportional to risk of venothromboembolic disease, comorbid medical conditions, and relative contraindications (e.g., active bleeding).
Tube feedings should be initiated within 5-7 days or sooner
(if patient is without PO intake).
Placement of a postpyloric feeding tube may decrease
gastric residuals and improve tolerance of enteral nutrition
and medications.
Pain (analgesia) and sedation management to be addressed
based on short- (<48 hours) or long- (>48 hours) term
anticipated needs, includes a daily drug holiday (refer to
pain and sedation order sets)
Consult physical medicine and physical therapy for patient
mobilization and decubitus ulcer prophylaxis as tolerated.
Pulmonary Dysfunction
Sepsis places extreme demands on the lungs, requiring a
high minute ventilation when the compliance of the respiratory system is diminished and muscle efficiency is impaired.
Respiratory failure may progress rapidly.
A sustained respiratory rate >30 breaths/minute (tachypnea)
or paradoxical breathing may be a sign of impending ventilatory collapse, even if PCO2 is normal.
Volume- or pressure-controlled mechanical ventilation with
an initial low tidal volume strategy (5-6 mL/kg based on
735
ideal body weight, not actual) should be started for those at

risk for or with evidence of acute lung injury or ARDS.
Limit volumes and airway pressures to decrease volumeand pressure-related overstretching of the alveoli.
Limit plateau pressure to <30-35 cm H2O pressure if possible
Positive end-expiratory pressure generally to start at 10 cm
H2O pressure
Use of corticosteroids is controversial and has not clearly
been shown to alter outcome related to ARDS or acute lung
injury.
Nitrous oxide, alprostadil, epoprostenol, surfactant, acetylcysteine, or ketoconazole has not been shown to be of clear
benefit.
Consider early tracheostomy for patients anticipated to
require prolonged ventilator support or have difficulty with
extubation.
Cardiovascular Failure
Shock is caused by inadequate supply or inappropriate use
of metabolic substrate (especially oxygen) and results in
ischemia, lactic acidosis, and tissue damage.
Circulatory adequacy is best assessed by mentation, urinary
output, skin perfusion, blood pressure, measurements of
oxygen delivery, oxygen consumption, and serum lactic acid
levels.
Blood pressure monitoring alone is insufficient for shock
assessment and management.
Value of monitoring central circulation through a pulmonary
artery catheter is unclear (use only in patients with refractory
shock, undetermined intravascular volume/hemodynamic,
or serious myocardial, pulmonary, or renal comorbid conditions).
Renal function decreases with mean arterial pressure generally
<60 mm Hg.
Septic shock (distributive) on presentation is characterized
by a low pulmonary capillary wedge pressure (<8 mm Hg),
normal to high cardiac index, and low systemic vascular
resistance before intravascular volume repletion.
Septic shock following intravascular volume resuscitation is
characterized by normal pulmonary capillary wedge pressure,
high cardiac index, and low systemic vascular resistance.
736
III DISEASES
Late septic shock with severe sepsis-related left ventricular

systolic dysfunction may demonstrate high pulmonary capillary wedge pressure, low cardiac index, and normal or high
systemic vascular resistance.
Crystalloid intravascular volume resuscitation (including
repeat boluses) is guided by clinical and objective measures,
as noted above.
Renal Dysfunction
Transient oliguria is common, but anuria is rare.
Obstructive uropathy has to be excluded.
Volume repletion often restores urinary output.
Acute renal failure requiring dialysis occurs in a small fraction of patients.
Transient hemofiltration often supports renal function
when necessary.
In most cases of sepsis-induced renal failure, renal function recovers.
The benefit of dopamine, diuretics, or fluid loading to prevent renal dysfunction in patients with volume repletion in
addition to volume repletion in normal blood pressure has not
been shown.
Patients with renal dysfunction who are to receive iodine
contrast (e.g., for CT, angiography) should be given acetylcysteine 600 mg PO or IV twice daily the day before the
contrast is administered and on the day it is given, with consideration also given to a bicarbonate infusion on the day of
administration or a single dose of theophylline.
Gastrointestinal Dysfunction
The liver is a mechanical and immunologic filter for portal
blood and may be a major source of cytokines that promote
the inflammatory cascade leading to the phenotypic SIRS
response.
For patients with normal liver function before sepsis, an
increase in liver enzymes is common, including mild
hyperbilirubinemia.
Frank hepatic failure is rare.
737
Septic shock usually causes ileus, which persists for 1-2

days and resolves after hypoperfusion has been corrected.
Delayed gastric emptying is common, especially early in
the natural course of diseases with sepsis
For stress ulcer prophylaxis, histamine antagonists, proton
pump inhibitors, or sucralfate is indicated, especially for
patients who require ventilatory support, have multiorgan
system failure, and cannot be fed enterally.
Coagulopathy
Subclinical coagulopathies, signified by mild increase in PT
or aPTT, decrease in platelet count, or moderate decrease in
plasma fibrinogen level, are common, but overt disseminated intravascular coagulopathy is less common.
Coagulopathy is caused by deficiencies of coagulation proteins, including protein C, antithrombin III, tissue-factor
pathway inhibitor, and the kinin system.
Laboratory findings are often a result of both a prothrombotic and thrombolytic intrinsic response to the SIRS
response.
Recombinant human activated protein C (drotrecogin alfa)
decreases mortality of patients who have sepsis.
Relative reduction of death, 19.4% (95% confidence interval, 6.6-30.5); absolute reduction of death, 6.1% (P=.005)
Risk of bleeding with protein C is only mildly increased
(3.5% vs. 2.0%, P=.06).
Dosage of drotrecogin alfa, 24 g/kg per hour for 96 hours
IV
Contraindications
Increased risk of bleeding
Profound thrombocytopenia
Drug Therapy
Initially, antibiotic coverage should accommodate the most
likely pathogens and include two or more agents with likely activity based on community or health care-associated
susceptibility profiles.
Dose adjustments are often required in renal and hepatic
insufficiency.
Be mindful of important interactions.
Aminoglycosides
738
III DISEASES
Increased nephrotoxicity with enflurane, cisplatin, and

possibly vancomycin
Increased ototoxicity with loop diuretics
Increased paralysis with neuromuscular blocking agent
Ampicillinincreased frequency of rash with allopurinol
Fluoroquinolonesprolonged QTc interval in the context of electrolyte abnormality or other cardioactive medications (e.g., selective antipsychotics or antiarrhythmics)
After culture results are available, treatment should be more
organism-specific
If cultures remain negative and clinical presentation is consistent with a noninfectious cause, antibiotics should be discontinued within 48-72 hours.
739
III DISEASES
URINARY TRACT INFECTIONS
William F. Marshall, M.D.
DEFINITIONS
Lower urinary tract (cystitis)urgency, frequency, dysuria,
and occasional suprapubic tenderness
Upper urinary tract (pyelonephritis)flank pain, chills, fever,
and, occasionally, urgency, frequency, dysuria, nausea, and
vomiting
Uncomplicated urinary tract infection (UTI)infection in a
host who has normal urinary tract anatomy and normal neurologic function
Complicated UTIinfection in a patient with structural
abnormalities of the urinary tract or abnormal neurologic
function (e.g., pregnant women, patients with spinal cord
injury, men with prostate obstruction, children)
Lower urinary tract symptoms alone do not rule out involvement of the upper urinary tract.
Classification
Upper and lower UTIs are compared in Table 1.
In studying Table 1, remember 2 important points:
There can be crossover of signs and symptoms between
lower and upper UTIs.
The listed signs and symptoms may occur in the absence
of any infection (e.g., symptomatic nephrolithiasis, nonspecific inflammation).
A detailed history and physical exam should direct clinical
suspicion.
It is useful to classify adults with UTI into the following five
groups:
Special abbreviations used in this chapter: DS, double strength; UTI, urinary tract
infection.
741
Young women with acute uncomplicated cystitis

Young women with recurrent cystitis
Young women with acute uncomplicated pyelonephritis
All adults with complicated UTI
All adults with asymptomatic bacteriuria (this chapter
does not consider young women with recurrent cystitis)
ETIOLOGY
Table 2 gives representative species and their approximate
rates of identification in UTIs in different classes of patients.
In as many as 10%-15% of symptomatic patients, bacteriuria
cannot be detected with routine lab methods:
Look for Neisseria gonorrhoeae and Chlamydia trachomatis and herpes simplex infection.
Anaerobes are rare.
Lactobacilli spp, Corynebacterium spp, and streptococci
are debatable.
EPIDEMIOLOGY
Risk factors for the development of UTI include
Recent sexual activity
Spermicidal or diaphragm use
History of recurrent UTI
Failure to urinate after sexual intercourse
Approximately 10%-20% of adult females will experience
symptomatic bacteriuria some time in their lifetime.
Frequency of UTI after a single catheterization is 1% for
outpatients and 10% for hospitalized patients.
Incidence of bacteriuria is equal among races.
Table 1. Comparison of Lower and Upper Urinary
Tract Infections (UTIs)
Lower UTI
Upper UTI
Suprapubic pain
Dysuria
Frequency
Urgency
Bacteriuria
Fever
Hematuria
Flank pain/tenderness
Fever
Bacteriuria
Nausea/vomiting
Dysuria
Frequency
Urgency
742
III DISEASES
Table 2. Cause of Urinary Tract Infections
Lower urinary tract, uncomplicated infection, outpatient
E. coli, % of cases
70-95
Staphylococcus saprophyticus,* % of cases
5-15
Upper urinary tract, complicated infection, inpatient
E. coli
Pseudomonas aeruginosa Candida spp
Proteus mirabilis Enterobacter spp
Morganella
Klebsiella spp
Enterococci
morganii
*Associated with spermicidal agents.
Especially with long-term catheterization
Frequency of significant bacteriuria (defined as >105 CFU)

for adults and the elderly is listed in Table 3.
Presenting signs and symptoms are listed in Table 1.
Elderly patients are mostly asymptomatic.
Confusion may be presenting sign in the elderly with UTI.
The elderly tend to have a higher incidence of bacteremia
in association with pyelonephritis than younger patients.
Bilateral papillary necrosis and progressive destruction of
the kidney occur more often in the elderly and in persons
with diabetes.
Be aware that bacteremia may occur in the absence of urinary
tract symptoms, especially in patients with an indwelling
urinary catheter.
Complications
Recurrent infectionOnce a woman develops UTI, she is
more likely to develop subsequent infections than a patient
who has had no previous infection.
Uncomplicated or recurrent UTIs in adults, in the absence of
obstruction, rarely if ever cause renal failure.
Perinephric abscess
Suspect this when fever does not resolve within 5 days
after IV antibiotic therapy.
743
Table 3. Prevalence of Significant Bacteriuria by Age

Group
Age group
Adults
Young, nonpregnant women
Pregnant women
Men
Elderly
Women
Men
Frequency, %
1-3
4-7
0.1
20-30
10
Most often, it is a contiguous infection with gram-negative

bacteria.
Intrarenal abscess
Most often blood-borne Staphylococcus aureus
Look for infections elsewhere (e.g., endocarditis,
osteomyelitis).
Emphysematous pyelonephritis
More common in diabetic patients
Almost always requires nephrectomy
70% mortality rate
Urosepsismore common in the elderly
Microscopic exam of urine for WBCs
Upper limit of normal5-10 WBCs per high-power field
Microscopic exam of urine for bacteria
One bacterium per oil-immersion field in midstream,
clean-catch, Gram-stained, urine specimen correlates with
105 bacteria per 1 mL of urine.
Dipstick WBC esterase
For >10 WBCs/mm3 urine, sensitivity of 75%-96% and
specificity of 94%-98%
Urinary dipstick for nitratessensitivity, 27%; specificity,
94%; negative predictive value, 87%
Diagnosis
For patients requiring hospitalization, always obtain cultures
of blood and urine before starting antibiotic therapy.
744
III DISEASES
Symptomatic infectionusually have at least 105 bacteria/mL urine

Asymptomatic bacteriuriatwo specimens to confirm the
diagnosis of infection
One clean-catch specimen with 105 bacteria/mL has 80%
positive predictive value for true infection.
Two specimens with 105 bacteria/mL of same organism
have a 95% positive predictive value.
Screen only for asymptomatic bacteriuria in adults before
urologic surgery and in pregnancy.
Urethral syndrome
Up to one-half of women with symptoms of lower UTI
have <105 bacteria/mL of urine.
This may represent an early phase in the infectious process;
genital herpes infection; chemical, allergic, or psychologic factors; fungi; urinary dilution before collection;
gram-positive organisms; or fastidious organisms.
No lab test reliably differentiates lower UTI from upper UTI.
Indwelling urinary catheters 102 CFU/mL of urine is
evidence of infection.
Virtually 100% of patients with an indwelling urinary catheter
will have bacteriuria within 30 days after catheter insertion.
Treat only when there are symptoms of infection (fever,
chills, etc.).
Treating asymptomatic infection in chronically catheterized patients invariably results in colonization or infection with progressively more antibiotic-resistant organisms.
TREATMENT
Aggressive hydration is not recommended.
Urinary analgesics or antiseptics have no role in routine management of symptomatic UTIs.
Empiric treatment should always be guided by Gram stain.
Gram-negative UTIs should be treated with fluoroquinolones, trimethoprim-sulfamethoxazone, or
cephalosporins.
Gram-positive UTIs should be given ampicillin (IV) or
amoxicillin (PO).
745
Acute Cystitis
Three days of treatment is more effective than single-dose
therapy and no different from 7-day therapy.
Fluoroquinolones are first choice of therapynorfloxacin
400 mg twice daily, ciprofloxacin 250 mg PO twice daily,
levofloxacin 500 mg PO daily.
Trimethoprim-sulfamethoxazole1 double strength (DS)
tablet PO twice daily in areas where prevalence of resistance is <20%
Acute Pyelonephritis
Mild to moderate, with normal or slightly elevated peripheral
WBC count, without nausea or vomiting, may begin oral
antibiotic therapy with a fluoroquinolone such as
ciprofloxacin 500 mg PO twice daily or levofloxacin 500
mg PO once daily for 7 days
If the organism is known to be sensitive, trimethoprimsulfamethoxazole, 1 DS tablet PO twice daily for 14 days
If enterococci are suspected (elderly men with prostate hypertrophy or obstruction) or known to be responsible, treat with
amoxicillin 500 mg PO 3 times daily for 14 days.
Severe, with increased peripheral WBC count, dehydration,
vomiting, fever, or evidence of sepsis, start IV antibiotic
therapy including a fluoroquinolone, a third-generation
cephalosporin, or piperacillin-tazobactam.
If a gram-positive organism is known to be responsible,
ampicillin-sulbactam or piperacillin-tazobactam with or
without an aminoglycoside is a reasonable empiric
choice.
Adjust antibiotic choices based on results of cultures and
susceptibilities when available.
Complicated UTI
Remove indwelling urinary catheter.
Start piperacillin-tazobactam, a third-generation cephalosporin, or fluoroquinolone.
Attempt to address underlying abnormalities such as obstruction or prostatitis.
If anatomic, functional, or metabolic abnormality cannot
be corrected, infection often recurs; thus, repeat culture in
1-2 weeks.
746
III DISEASES
Asymptomatic Bacteriuria and Bacteriuria of Pregnancy
Therapy is not indicated for asymptomatic bacteriuria in an
adult except in cases of urinary tract obstruction and/or
pregnancy.
Remember, there is no urgency to begin treatment and two
cultures should be obtained to confirm the presence of bacteriuria before instituting antibiotic therapy.
Generally, 7 days of amoxicillin, amoxicillin-clavulanate,
cephalexin, or a sulfonamide eradicates bacteriuria in 70%80% of patients.
Sulfonamides should be avoided in the first trimester and
the last few weeks of pregnancy.
Avoid tetracyclines and quinolones throughout pregnancy.
If the isolated organism is resistant to all nontoxic antibiotics, treatment should not be instituted in nonobstructed
patients.
747
III DISEASES
VASCULITIS
Peter D. Kent, M.D.
Thomas G. Mason II, M.D.
DEFINITION
A group of diseases caused by inflammation of blood vessel
walls
CLASSIFICATION
An arbitrary classification is by the size of the vessel or vessels involved (Table 1).
The predominantly pediatric vasculitic syndromes of
Kawasaki disease and Henoch-Schnlein purpura are not
considered in this chapter.
ETIOLOGY
The cause is often unknown.
It may be secondary to infection or malignancy.
Immune complexes or antibodies, such as antineutrophil
cytoplasmic antibodies (ANCAs) may be pathogenic.
Interaction of endothelial cells with lymphocytes and
cytokines is integral in the pathogenesis of many vasculitic
syndromes.
Presentation varies greatly depending on type of vasculitis.
Systemic constitutional symptoms such as fever, weight loss,
night sweats, myalgias, arthralgias, and malaise are common.
Patients with large- and medium-artery vasculitis may have
large-artery bruits.
Hypertension may reflect renal involvement.
Special abbreviations used in this chapter: ANCA, antineutrophil cytoplasmic antibody (c, cytoplasmic; p, perinuclear); CRP, C-reactive protein; MRA, magnetic resonance angiography.
749
750
Table 1. Vasculitic Syndromes According to Blood Vessel Size

Vessels most commonly involved
Vasculitic syndrome
Takayasu arteritis
Giant cell (temporal)
arteritis
Polyarteritis nodosa
Primary central
nervous system
vasculitis
Churg-Strauss
syndrome
Microscopic polyangiitis
Vasculitis &
connective tissue
diseases
Cryoglobulinemic
vasculitis
Cutaneous vasculitis
Aorta & primary

branches
Large & medium

arteries
Medium & small

muscular arteries
Arterioles
Capillaries
& venules
III DISEASES
Complications
Vasculitis can cause many debilitating complications, including neuropathies, thromboses, tissue ischemia, hemorrhage,
cognitive changes, and renal impairment.
ESR and C-reactive protein (CRP) are increased in most
vasculitic syndromes.
Anemia of chronic disease, thrombocytosis, and low albumin
are frequent.
HIV testing and syphilis screening should be considered for
patients with risk factors.
Complement levels may be low in patients with immune
complexmediated vasculitis (cryoglobulinemia or vasculitis
associated with connective tissue diseases).
Complement levels are normal or high in giant cell arteritis,
microscopic polyangiitis, and polyarteritis nodosa.
Urinalysis may suggest renal involvement with microhematuria, proteinuria, or RBC casts.
Chest X-ray may show pulmonary nodules with cavitation
(often in Wegener granulomatosis), alveolar infiltrates of
pulmonary hemorrhage, or chronic eosinophilic pneumonia
in Churg-Strauss syndrome.
EMG may be useful in the setting of mononeuritis multiplex or inflammatory myopathies.
Many forms of large-vessel vasculitis can be diagnosed with
arteriography.
Magnetic resonance angiography (MRA) may be a less
invasive alternative.
Biopsy is an excellent tool in the diagnosis of vasculitis.
The focal and segmental features of many types of vasculitis
must be considered when evaluating biopsy specimens.
Biopsy of symptomatically involved areas such as muscle,
sural nerve, skin, or testis may be diagnostic.
MANAGEMENT
Therapy depends on type and severity of vasculitis.
Immunosuppressive medications are often used.
751
SPECIFIC DISEASE ENTITIES

Takayasu Arteritis
Definition
Granulomatous arteritis of aorta and its major branches
Etiology
Unknown
Epidemiology
Young women <50 years, particularly of Asian or Eastern
European background
Claudication in arms and legs and diminished or unequal
peripheral pulses
Bruits over large arteries
Symptoms of central nervous system vascular insufficiency,
including headaches, dizziness, amaurosis, transient ischemic
attacks, and stroke
Angina pectoris can occur if the ostia of the coronary arteries become narrowed.
Mesenteric ischemia and hypertension can develop from
narrowing of visceral and renal arteries.
Complications
Ischemia of brain, viscera, and extremities
Aortic regurgitation or dissection
Assess acute phase reactants (ESR, CRP).
Aortography shows long-segment smooth narrowings or
complete occlusions.
MRA detects increased arterial wall thickness.
Histology shows focal panarteritis.
Management
Corticosteroids and cytotoxic drugs (cyclophosphamide and
methotrexate)
Angioplasty, vascular bypass surgery, or aortic valve replacement may be necessary.
752
III DISEASES
Giant Cell (Temporal) Arteritis
Definition
Granulomatous arteritis of the aorta and its major branches,
with predilection for extracranial branches of the carotid
artery, particularly the temporal arteries
Etiology
Unknown
Epidemiology
Most patients are of Northern European descent.
More common in women (2:1)
Age at onset, 50 years (mean, 72 years)
Constitutional symptoms often with fever >39C
Criteria for polymyalgia rheumatica
Age >50 years
ESR >40 mm/hour
Pain and morning stiffness for 30 minutes in at least
2 of the following: shoulder girdle, hip girdle, neck,
or torso
Symptoms present for at least 1 month
Headache, jaw claudication, scalp tenderness, visual symptoms, and cough or sore throat indicate cranial artery involvement by giant cell arteritis.
Many patients have tender, nodular temporal arteries, sometimes without a pulse.
Involvement of the aortic arch (aortic arch syndrome) and its
primary branches may cause symptoms of arm claudication,
diminished blood pressure, or cerebral ischemia.
Complications
Visual loss, often permanent
Aortic arch syndrome, which involves smooth narrowing
of the aorta or its primary branches
Acute aortic dissection or aortic aneurysms are uncommon and late complications.
753
ESR averages 80-100 mm/hour (Westergren)
Diagnosis is confirmed with temporal artery biopsy specimen
showing transmural inflammation with mononuclear cells,
histiocytes, and multinucleated giant cells.
If the biopsy specimen from the first side is negative, a
specimen should be obtained from the other side.
Management
Giant cell arteritis generally is treated with oral prednisone,
40-60 mg/day in divided doses.
Continue 40 mg/day for 2-4 weeks until the ESR is normal.
Prednisone dose usually can be reduced by 5 mg every week
until a 20-mg/day dose is reached, with careful monitoring
of symptoms and ESR.
If the dose is <20 mg/day, it is usually reduced by 2.5 mg per
month as tolerated by symptoms and ESR.
If the dose is <5 mg/day, it is reduced by 1 mg per month.
Polyarteritis Nodosa
Definition
Necrotizing inflammation of medium-sized or small arteries
without glomerulonephritis or vasculitis in arterioles, capillaries, or venules
Etiology
May be a consequence of hepatitis B infection (7% of
patients), HIV, cytomegalovirus, parvovirus B19, human
T-lymphotropic virus 1, or hepatitis C infection
Epidemiology
Occurs equally in men and women
Age at onset, usually in 40s and 50s
Constitutional symptoms
Neurologicmononeuritis multiplex (70% of patients)
Skinlivedo reticularis, skin ulcers, purpura
Cardiaccongestive heart failure
Gastrointestinalabdominal pain, bleeding, perforation
Renalmultiple infarcts
754
III DISEASES
Musculoskeletalmyalgias and arthralgias

Orchitis is common.
Pulmonary involvement is rare.
Complications
Mononeuritis multiplex, intestinal ischemia, and renal
infarcts, with the latter two being the leading causes of death
Aneurysms are at risk for rupture.
With treatment, 5-year survival is 60%-80%.
Hepatitis B surface antigen and antibody should be checked.
ANCAs are rare.
Mesenteric angiography often shows both microaneurysms
and stenoses in medium-sized vessels.
Biopsy specimens from skeletal muscle, sural nerve, kidney, testis, liver, or rectum show focal segmental necrotizing
vasculitis.
Management
Methylprednisolone, 30 mg/kg IV every 24 hours for 3
days, then prednisone at 1 mg/kg per day tapered over 9-12
months
Pulse cyclophosphamide, 0.6 g/m2, delivered monthly for
6-12 months and then every 2-3 months
Aggressive hydration and sodium 2-mercaptoethanesulfonate (mesna) are used during pulse therapy.
Oral cyclophosphamide, 100-150 mg/day, may be used
instead of pulse dosing for less severe cases, and it is steroidsparing.
In hepatitis Brelated disease
Administer corticosteroids to stabilize life-threatening
symptoms.
Administer antiviral therapy for hepatitis.
Primary Central Nervous System Vasculitis

Definition
Necrotizing and/or granulomatous vasculitis affecting predominantly leptomeningeal and cortical vessels
755
Etiology
Primary angiitis of the central nervous system has no known
cause.
Secondary angiitis of the central nervous system may result
from another systemic vasculitic syndrome, an infection, a
neoplasm, or a drug.
Epidemiology
Age at onset, usually in the 20s or 30s
Headaches and focal and nonfocal neurologic deficits
Decreased cognitive function or fluctuating level of
consciousness
Constitutional symptoms are uncommon.
Complications
Strokes, seizures, cognitive decline
ESR is frequently normal.
MRI may show multiple bilateral, supratentorial infarcts.
Leptomeninges may enhance with contrast.
Angiography can show a beading pattern of alternating
stenoses and dilatations.
CSF may have increased opening pressure, mildly increased
protein level, and pleocytosis.
Pathology shows segmental necrotizing and frequently granulomatous vasculitis that affects predominantly leptomeningeal and cortical blood vessels.
Management
PO or pulse cyclophosphamide in combination with corticosteroids
Churg-Strauss Syndrome
Definition
Granulomatous arteritis of small- and medium-sized vessels
associated with asthma, pulmonary infiltrates, and eosinophilia
Etiology
Unknown
756
III DISEASES
Epidemiology
Mean age at onset, between 38 and 48 years.
Pulmonaryasthma (93% of patients) or allergic rhinitis,
often present for years before onset of vasculitis
Infiltrates may be seen on chest X-ray.
Neurologicmononeuritis multiplex (53%-75% of patients)
Skinpurpura and SQ nodules
Cardiaccardiomyopathy and pericarditis
Gastrointestinaldiarrhea, bleeding, abdominal pain
Renalfocal segmental glomerulonephritis with necrotizing
features
Musculoskeletalpolyarthralgias and arthritis
Complications
Neuropathy, cardiomyopathy, renal impairment
Five-year survival rate with treatment is about 82%.
Eosinophilia >109/L on CBC
Associated with ANCA (59% of patients), particularly
antimyeloperoxidase positivity
Eosinophils or extravascular eosinophilic granulomas in
biopsy specimen
Management
Wegener Granulomatosis
Definition
Granulomatous inflammation of upper and lower respiratory tract and necrotizing vasculitis of small- and mediumsized vessels, often causing glomerulonephritis
Etiology
Unknown
757
Epidemiology
Affects both sexes equally
More common in whites
Mean age at onset, 41 years; range, 9-78 years
Systemic constitutional symptoms
Epistaxis, saddle nose deformity, nasal septal perforation or
ulceration, pain over the sinuses
Subglottic lesions and stenosis
Hypertension or hematuria
Pulmonary symptoms such as cough, dyspnea, hemoptysis,
and chest pain (60%-80% of patients)
Complications
Subglottic stenosis may require dilatation or tracheostomy
Renal failure
With treatment, 5-year survival rate is about 70%.
Assess acute phase reactants (ESR, CRP).
Cytoplasmic ANCA (c-ANCA) and anti-proteinase 3 are
both sensitive (80%) and specific (97%) for Wegener granulomatosis.
The c-ANCA titer correlates with disease activity in about 2/3
of patients.
Perinuclear ANCA (p-ANCA) is rarely associated with
Wegener granulomatosis (1% of patients).
Necrotizing granulomas are seen on biopsy specimens.
Management
Trimethoprim-sulfamethoxazole, 160 mg/800 mg, twice
daily decreases incidence of relapse.
Methotrexate is another treatment option for selected
patients.
It is used occasionally for cyclophosphamide sparing.
Microscopic Polyangiitis
Definition
Necrotizing pauciimmune deposits (few or no immune
758
III DISEASES
deposits) affecting small vessels, commonly causing glomerulonephritis
Etiology
Unknown
Epidemiology
Mean age at onset, about 50 years
RenalMicroscopic hematuria and proteinuria are nearly
always present (>90% of patients).
Unlike polyarteritis nodosa, pulmonary involvement may
occur in microscopic polyangiitis.
Pulmonary hemorrhage and hemoptysis may occur (12%29% of patients).
Abdominal and musculoskeletal pain, gastrointestinal tract
bleeding, or peripheral neuropathy may be present.
Skin lesions (purpura, splinter hemorrhages) are found in
50% of patients.
Complications
Pulmonary hemorrhage, renal failure
With treatment, 5-year survival is 65%
Relapse rate is 38%.
Eosinophilia in 14% of patients
Normal whole complement and C3 and C4 levels
Impaired renal function
p-ANCA in 61% of patients and c-ANCA in 15%
Most ANCAs are antimyeloperoxidase p-ANCA
Positive predictive value of positive p-ANCA in these patients
is only 12%.
On arteriography, microaneurysms and/or stenoses are
rare.
Renal biopsy specimen may show segmental thrombosis and
necrotizing crescenteric glomerulonephritis.
Other possible biopsy sites include the skin and sural nerve.
759
Small-vessel involvement is required and excludes the diagnosis of polyarteritis nodosa.
Management
Cryoglobulinemic Vasculitis
Definition
Cryoglobulins are monoclonal or polyclonal immunoglobulins that precipitate at cold temperatures and may produce
vasculitis.
Classification
Cryoglobulin without underlying disease is essential cryoglobulinemia.
Type Imonoclonal cryoglobulin (IgM, IgG, etc.)
Usually associated with underlying lymphoproliferative or
myeloproliferative disorder
Rarely causes vasculitis
Type IImixed cryoglobulins with a monoclonal (usually
IgM) and polyclonal (usually IgG) component
Associated with lymphoproliferative diseases, autoimmune diseases, and infections
Type IIImixed polyclonal cryoglobulins
Associated with lymphoproliferative diseases, autoimmune diseases, and bacterial infections
Etiology
Cryoglobulins deposit in blood vessel walls and induce complement activation, causing tissue damage and recruitment of
inflammatory cells.
Hepatitis C infection, other infections, connective tissue diseases, and myeloproliferative and lymphoproliferative disorders can induce cryoglobulins.
Epidemiology
Average age at onset, about 50 years
Mixed cryoglobulins are present in >50% of patients with
hepatitis C infection, but vasculitis occurs only in a small
fraction of patients.
760
III DISEASES
Purpura, cutaneous ulceration, and arthritis or arthralgia
(>70% of patients)
Peripheral neuropathy (40%-70%)
Renal involvement (<40%)
Cryoglobulinemic glomerulonephritis occurs mainly with
type II mixed cryoglobulinemia and causes chronic renal
insufficiency in 50% of patients.
Renal vasculitis of small- and medium-sized renal arteries occurs in 33% of patients with cryoglobulinemic
glomerulonephritis.
Complications
Renal insufficiency
Prognosis is related to underlying disease.
Antihepatitis C antibodies (90% of patients), hepatitis C
RNA (85%)
Antihepatitis B antibodies (40%), hepatitis B surface antigen (4%)
Aminotransferase levels are increased in 25%-40% of patients.
Serum protein electrophoresis, immunofixation, and cryoglobulins
Complement levels (hypocomplementemia in 90%)
Rheumatoid factor in >70% of patients.
Antinuclear antibody (20%), extractable nuclear antigen
(8%), ANCA (<5%)
With immunofluorescence, biopsy specimens show deposition of mixed cryoglobulins and complement in walls of
small vessels.
Bone marrow biopsy may be needed to rule out underlying
myeloproliferative or lymphoproliferative disorder.
Management
The underlying disease should be treated.
If no underlying disease is found, treat with methotrexate, azathioprine, or interferon alfa.
Acute exacerbations of hepatitis Cassociated cryoglobu
761
linemic vasculitis often require both corticosteroids and PO

or pulse cyclophosphamide.
Interferon alfa is not recommended for acute exacerbations.
Interferon alfa should be used after remission has been
achieved.
Ribavirin may also be considered.
Plasmapheresis may help in severe cases.
Cutaneous Vasculitis
Definition
Vasculitis causing visible skin lesions
Classification and Etiology
Leukocytoclastic vasculitisnecrotizing vasculitis with fibrinoid necrosis and leukocytolysis involving postcapillary
venules
May be secondary to underlying systemic vasculitis, connective tissue disease, or malignancy
Hypersensitivity vasculitis
Usually secondary to drugs
Requires exclusion of other causes of leukocytoclastic
vasculitis
Palpable purpura, often on lower extremities
Urticaria, ulcerations, nodular lesions
Complications
Related to underlying disease process
Skin biopsy can confirm leukocytoclastic vasculitis with
involvement of dermal postcapillary venules.
Immunofluorescence studies may show immunoglobulin
and C3 deposition.
Testing for systemic vasculitis, connective tissue disease,
and malignancy should be done as clinically indicated.
Management
Treat the underlying disease.
With hypersensitivity vasculitis, discontinue the offending drug.
Treat with prednisone or dapsone.
762
IV THERAPY
ANTIMICROBIAL AGENTS
John W. Wilson, M.D.
Lynn L. Estes, Pharm.D.
GENERAL PRINCIPLES
Factors to Consider Before Initiating Antimicrobial
Therapy
Define the hostmany types of infection and rates of
disease progression are influenced by host factors, including
medical history, immunosuppression, patient age, absence of
spleen, concurrent medications, recent or current hospitalization, contacts with infectious persons or animals and travel
history.
Define the infection syndromelocation of infection, rate
of progression, severity of infection (i.e., localized vs. multiorgan involvement or hemodynamic instability)
Define the microbiologyantimicrobial therapy (when
possible) should be directed in a targeted fashion against
identified or suspected organisms causing infection and
should reach the site of infection.
Other Considerations
Identify infections requiring emergent medical or surgical
intervention: meningitis, septic shock, fasciitis, myonecrosis, others.
Identify syndromes requiring prompt intervention: neutropenic gram-negative bacteremia, empyema, cholangitis
biliary obstruction, complex vascular catheter infections
Particular attention should be paid to the Gram stain, culture,
and antimicrobial susceptibilities of fluid or tissue samples
submitted to the microbiology laboratory to help direct
antimicrobial therapy.
Special abbreviations used in this chapter: CMV, cytomegalovirus; CNS, central

nervous system; GI, gastrointestinal; HHV, human herpesvirus; HSV, herpes
simplex virus; VZV, varicella-zoster virus.
763
Patient drug allergies and organ function are critical to identify

and monitor for optimal selection and dosing of antimicrobial therapy.
Infectious disease consultation should be obtained for all
serious and complex infections.
ANTIBACTERIAL AGENTS
Penicillins (Table 1)
Prototypic Agents
Natural penicillinspenicillin G
Aminopenicillinsampicillin, amoxicillin, ampicillinsulbactam (Unasyn), amoxicillin-clavulanate (Augmentin)
Penicillinase-resistant penicillinsnafcillin, oxacillin,
dicloxacillin
Carboxypenicillins/ureidopenicillinsticarcillin, piperacillin,
ticarcillin-clavulanate (Timentin), piperacillin-tazobactam
(Zosyn)
Table 1. Penicillins
Drug
Amoxicillin
Amoxicillinclavulanate
Ampicillin IV
Ampicllinsulbactam
Dicloxacillin
Nafcillin
Oxacillin
Penicillin G
IV
Penicillin V
PO
Piperacillin
Pipieracillintazobactam
Ticarcillinclavulanate
Usual adult dose with normal

renal function
Elimination
250-500 mg tid, 875 mg bid

250-500 mg tid, 875 mg bid
Renal*
Renal*
1-2 g q 4-6 hours

1.5-3 g q 6-8 hours
Renal*
Renal*
125-500 mg qid
1-2 g q 4-6 hours
1-2 g q 4-6 hours
5-24 mU daily divided
q 4 hours or continuous
infusion
250-500 mg tid or qid
Hepatic/biliary
Hepatic/biliary
Hepatic/biliary
Renal*
3-4 g q 4-6 hours

3.375-4.5 g q 6 hours
Renal*
Renal*
3.1 g q 4-6 hours
Renal*
Renal*
bid, twice daily; q, every; qid, 4 times daily; tid, 3 times daily.
*Modify dose for renal dysfunction.
764
IV THERAPY
Spectrum of Activity
Natural penicillinsmost streptococci and enterococci; most
Neisseria gonorrhoeae, susceptible anaerobes (Clostridium
spp, most oral Bacteroides, Fusobacterium, Peptostreptococcus),
Listeria, Pasteurella, Treponema pallidum (syphilis), Borrelia
burgdorferi (the species for Lyme disease)
Most staphylococci and gram-negative organisms produce lactamase that renders these agents inactive.
Aminopenicillinsmost streptococci, enterococci, many
Escherichia coli, Proteus mirabilis, Salmonella, Shigella,
-lactamasenegative Haemophilus influenzae
Addition of a -lactamase inhibitor (Augmentin, Unasyn)
extends the spectra to include -lactamaseproducing but
methicillinsensitive staphylococci, Bacteroides fragilis,
and -lactamaseproducing strains of H. influenzae and
Moraxella catarrhalis.
Penicillinase-resistant penicillinsnarrow spectrum
Includes methicillin-susceptible staphylococcus and group
A streptococci
Useful for serious staphylococcal infections and skin or soft
tissue infections
No gram-negative, enterococcal, or anaerobic activity
Carboxypenicillins/Ureidopenicillins
Many gram-negative bacteria, including most Enterobacteriaceae and most Pseudomonas aeruginosa
Compared with penicillin G, they are slightly less active
against streptococci and enterococci.
Addition of a -lactamase inhibitor (Zosyn and Timentin)
extends the spectra to methicillin-sensitive staphylococci
and B. fragilis; Timentin has activity against many
Stenotrophomonas.
Used when broad-spectrum empiric therapy is needed and
for gram-negative and mixed nosocomial infections
Toxicities
Hypersensitivity reactions, gastrointestinal (GI) side effects
(nausea, vomiting, diarrhea, and Clostridium difficile),
phlebitis with IV therapy
765
High-dose IV penicillincan cause central nervous system

(CNS) side effects, including seizures (especially without
renal dose adjustment); hyperkalemia (potassium salt) or
hypernatremia (sodium salt)
Penicillinase-resistant penicillinscan cause interstitial
nephritis, phlebitis, hepatitis, and neutropenia with prolonged
use
Ticarcillin and Timentincan cause sodium overload,
hypokalemia, platelet dysfunction
Cephalosporins (Table 2)
Prototypic Agents
First generation: cefazolin, cephalexin
Second generation: cefuroxime, cefoxitin, cefotetan, cefaclor, cefprozil, loracarbef
Table 2. Cephalosporins
Drug
Cefaclor
Cefadroxil
Cefazolin
Cefdinir
Cefepime
Cefixime
Cefotaxime
Cefotetan
Cefoxitin
Cefpodoxime
Cefprozil
Ceftazidime
Ceftibuten
Ceftriaxone
Cefuroxime
IV
Cefuroxime
axetil PO
Cephalexin
Usual adult dose with

normal renal function
Elimination
250-500 mg tid
500 mg-1 g bid
1-2 g q 8 hours
300 mg bid
1-2 g q 8-12 hours
400 mg daily
1-2 g q 8 hours
1-2 g q 12 hours
1-2 g q 6-8 hours
200-400 mg bid
250-500 mg bid
1-2 g q 8 hours
400 mg daily
1-2 g q 24 hours
750-1,500 mg q 8 hours
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal*
Renal/hepatobiliary
Renal*
250-500 mg bid
Renal*
250 mg-1 g qid

Renal*
bid, twice daily; q, every; qid, 4 times daily; tid, 3 times daily.
*Modify dose for renal dysfunction.
766
IV THERAPY
Third generation: cefotaxime, ceftriaxone, ceftazidime,

cefpodoxime, cefixime
Fourth generation: cefepime
First generation
Highly active against methicillin-susceptible staphylococci, -hemolytic streptococci, and many strains of P.
mirabilis, E. coli, and Klebsiella spp.
Used commonly for methicillin-sensitive staphylococcal
infections and skin and soft tissue infections
Second generation
Improved gram-negative activity but slightly less grampositive activity than first-generation agents
Cefuroxime and the oral agentsactivity against community-acquired respiratory pathogens (Streptococcus
pneumoniae, H. influenzae, M. catarrhalis)
Cefotetan and cefoxitingram-negative and anaerobic
activity; have been used for obstetrics/gynecologic and
colorectal surgical prophylaxis and treatment of community-acquired abdominal infections and pelvic inflammatory disease
Third generation
Improved gram-negative activity vs. first- and secondgeneration agents
Cefotaxime and ceftriaxoneenhanced gram-negative
activity compared with second-generation agents but not
active against Pseudomonas; good activity against community-acquired respiratory, urinary, and meningeal
pathogens
Ceftazidimeless active against staphylococci and streptococci but has activity against P. aeruginosa
Fourth generation
Cefepimehighly active and durable gram-negative
activity (including P. aeruginosa) and enhanced grampositive activity (methicillin-susceptible S. aureus and
Streptococcus spp)
767
Toxicities
GI effects (nausea, vomiting, and diarrhea) are most common.
Hypersensitivity reactions (cross-reactivity with penicillins,
about 5%), drug fever, and C. difficile colitis
Cefotetan and cefamandole (N-methylthiotetrazole side
chain)associated with hypoprothrombinemia (increased
INR) and a disulfiram-like reaction when ethanol is consumed
Ceftriaxoneassociated with pseudocholelithiasis, cholelithiasis, and biliary colic, especially in young children
Monobactam
AgentAztreonam
Gram-negative aerobic organisms, including most P.
aeruginosa
Toxicities
Similar to other -lactams
Because of low risk of cross-allergenicity, it can often be
used in patients with penicillin or cephalosporin allergies.
Carbapenems (Table 3)
AgentsImipenem, Meropenem, Ertapenem
Spectrum
Very broad antibacterial activity, including gram-positives,
gram-negatives, and anaerobes
Gram-positive spectrum includes -hemolytic streptococci,
S. pneumoniae, and methicillin-susceptible S. aureus;
imipenem and meropenem cover susceptible Enterococcus
spp, but ertapenem is inactive.
Gram-negative spectrum includes the Enterobacteriaceae
(including those with extended-spectrum -lactamase production), H. influenzae, and M. catarrhalis; meropenem and
imipenem cover most P. aeruginosa and Acinetobacter spp,
but, ertapenem is inactive against both.
Anaerobic activity is excellent and includes Bacteroides,
Clostridium, Fusobacterium, Peptostreptococcus, and
Prevotella.
768
IV THERAPY
Table 3. Carbapenems
Drug
Ertapenem
Imipenem
Meropenem
Usual adult dose

for normal
renal function
Elimination
1 g q 24 hours
500 mg q 6 hours
1-2 g q 8 hours
Renal*
Renal*
Renal*
q, every.
Toxicities
Can cause GI side effects, hypersensitivity reactions (may
be cross-allergenic with penicillins), drug fever, and overgrowth of resistant organisms (yeast, Stenotrophomonas,
C. difficile)
Seizures occur rarely with these agents, but occur especially with a history of seizure disorder, renal insufficiency without proper dosage adjustment, or structural CNS defects.
Aminoglycosides (Tables 4 and 5)
Prototypic Agents
Gentamicin, tobramycin, amikacin, streptomycin
Includes most aerobic gram-negative bacilli, mycobacteria
(varies by agent), Brucella (streptomycin), Nocardia
(amikacin), Francisella tularensis (streptomycin), Yersinia
pestis (streptomycin)
Gentamicin and streptomycin are synergistic with certain lactams and vancomycin against susceptible enterococci
(gentamicin, streptomycin), staphylococci, and several aerobic
gram-negatives.
Toxicities
Can cause nephrotoxicity, auditory or vestibular toxicity,
and rarely neuromuscular blockade
769
770
Table 4. Aminoglycoside Dosing for Normal Renal Function*

Condition
Gentamicin/tobramycin
traditional dosing
Pneumonia/sepsis
2-2.5 mg/kg q 8 hours
Bacteremia, SSTI,
pyelonephritis
Lower urinary tract
infection
Gram-positive synergy
1.5-1.7 mg/kg q 8 hours

1-1.3 mg/kg q 8 hours
1 mg/kg q 8 hours
pk, peak; SSTI, skin & soft tissue infection; tr, trough.
*Must adjust doses and intervals for renal dysfunction.
Serum level
targets, g/mL
Amikacin/strepto
traditional dosing
pk: 7-10
tr: <1.2
pk: 6-8
tr: <1.2
pk: 4-5
tr: <1.2
pk: 3-4
tr: <1.2
7-8 mg/kg q 8-12 hours

6 mg/kg q 8-12 hours
5-6 mg/kg q 8-12 hours
--
Serum level targets,

g/mL
pk:
tr:
pk:
tr:
pk:
tr:
25-40
2.5-8
20-30
2.5-4
15-20
2.5-4
--
IV THERAPY
Table 5. Single Daily (Pulse) Dosing*
Gentamicin/tobramycin 5-7 mg/kg daily
Amikacin/streptomycin 15-20 mg/kg daily
*Adjust dosing interval for renal dysfunction.
Nephrotoxicitythe risk is enhanced in presence of other

nephrotoxins and is usually reversible; monitoring drug levels
is important to minimize this.
Ototoxicitymay be irreversible
Vancomycin
Includes most aerobic and anaerobic gram-positive organisms
Active against methicillin-resistant staphylococci, susceptible
enterococci, and highly penicillin-resistant S. pneumoniae
An alternative agent for infections caused by methicillinsensitive staphylococci (less active than cefazolin, nafcillin,
oxacillin), ampicillin-sensitive enterococci or streptococci
in patients intolerant of -lactam antimicrobials
Not active against certain strains of Lactobacillus,
Leuconostoc, Actinomyces, and vancomycin-resistant
enterococci
Use should be minimized because of emergence of vancomycin-resistant enterococci and, more recently, vancomycin-resistant staphylococci
Oral vancomycin is not systemically absorbed and can be
used for treatment of C. difficile colitis.
Toxicities
Rare ototoxicity and nephrotoxicity (especially in combination with other nephrotoxins)
Infusion-related pruritus and rash or flushing reaction involving face, neck, and upper body (red-man or red-neck
syndromenot an allergic reaction) can be minimized by
prolonging the infusion and/or administering an antihistamine.
771
Dosing
Usual dosing is 15-20 mg/kg every 12 hours with normal
renal function.
Dose should be decreased or interval prolonged for renal
dysfunction.
Target trough levels are 5-15 g/mL for most infections.
Troughs of 15-20 g/mL may be appropriate for methicillinresistant S. aureus pneumonia or meningitis.
Fluoroquinolones (Table 6)
Prototypic Agents
Ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin,
gemifloxacin
Active against most aerobic gram-negative bacilli, including the Enterobacteriaceae, H. influenzae, and some staphylococci; gram-positive and anaerobic activity varies
Ciprofloxacin has the best activity against P. aeruginosa but
does not have good activity against S. pneumoniae, and
clinical failures have been reported.
Levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin
have improved activity against S. pneumoniae and other
gram-positive organisms; they also have good activity
against atypical pneumonia pathogens such as Chlamydia
Table 6. Fluoroquinolones
Drug
Ciprofloxacin IV
Ciprofloxacin PO
Gatifloxacin IV/PO
Gemifloxacin PO
Levofloxacin IV/PO
Moxifloxacin IV/PO
Usual adult dose

with normal
renal function
200-400 mg q 12 hours
400 mg q 8 hours
250-750 mg q 12 hours
400 mg daily
320 mg daily
250-750 mg daily
400 mg daily
q, every
*Adjust doses for renal function.
772
Elimination
Renal*
Renal*
Renal*
Fecal/renal*
Renal*
Hepatic/renal
(minor)
IV THERAPY
pneumoniae, Mycoplasma pneumoniae, and Legionella

and thus are useful for community-acquired respiratory
infections.
Moxifloxacin, gatifloxacin, and gemifloxacin have appreciable anaerobic activity but are not drugs of choice for
serious anaerobic infections.
Toxicities
GI effects, including C. difficile colitis
Rash is most frequent with gemifloxacin.
CNS effects are rare but can include seizures in patients predisposed, especially when not dose adjusted for renal function.
Erosions have been seen in cartilage in animals; thus,
quinolones generally are not recommended in pregnant
women or in patients younger than 18 years.
Tendinitis and tendon rupture are rare complications.
QT prolongation and rare cases of torsades de pointes have
been reported.
Gatifloxacin: hyper- and hypoglycemia have been reported
Oral chelating agents such as aluminum, calcium, magnesium, iron, and zinc will bind fluoroquinolones and inhibit
absorption. Such drugs should not be given together.
Tetracyclines and Glycylcycline (Tigecycline) (Table 7)

Prototypic Agents
Tetracycline, doxycycline, minocycline, tigecycline
Includes Rickettsia, Chlamydia, M. pneumoniae, Vibrio,
Brucella, B. burgdorferi (early stages), Helicobacter pylori,
many S. pneumoniae
Minocycline is also active against methicillin-resistant
staphylococci (for mild disease in patients who cannot tolerate vancomycin), Stenotrophomonas, and Mycobacterium
marinum
Tigecycline is active against several multidrug resistant
organisms, including several that are tetracycline resistant.
773
Table 7. Tetracyclines and Tigecycline

Drug
Usual adult dose
Elimination
Doxycycline IV/PO
Minocycline IV/PO
Tetracycline PO
Tigecycline IV
200 mg 1, 100 mg bid

250 mg 1, 100 mg bid
250-500 mg qid
100 mg 1, 50 mg q
12 hours
Biliary/renal
Biliary/renal
Renal*/biliary
Biliary-fecal/
renal
bid, twice daily; q, every; qid, four times daily.

*Adjust tetracycline dose for renal function or use alternative agent.
Gram-positive activity includes methicillin-sensitive and

resistant staphylococci, and vancomycin-resistant
enterococci
Gram-negative activity is broad, including E. coli, Klebsiella,
Enterobacter, Citrobacter, Acinetobacter, Stenotrophomonas,
Haemophilus, and Moraxella. It does not have appreciable
activity against Proteus or Pseudomonas.
Good anaerobic and non-tuberculosis mycobacterial
activity
Toxicities
Include GI effects (especially prominent with tigecycline),
rash, photosensitivity
Avoid in pregnant females and children because these
agents impair bone growth of the fetus and stain the teeth
of children.
Coadministration of antacids, iron, calcium, magnesium, or
aluminum substantially decreases the enteric absorption of
PO agents.
Macrolides and Ketolide (Telithromycin) (Table 8)

Prototypic Agents
Erythromycin, clarithromycin, azithromycin, telithromycin
Most -hemolytic streptococci, S. pneumoniae (resistance
is increasing), some methicillin-sensitive staphylococci, B.
pertussis, Campylobacter jejuni, Treponema pallidum,
Ureaplasma, M. pneumoniae, L. pneumophila, Chlamydia sp
774
IV THERAPY
Table 8. Macrolides and Telithromycin
Drug
Azithromycin
Clarithromycin
Erythromycin
Telithromycin
Usual adult dose

PO: 250-500 mg daily
IV: 500 mg daily
PO: 250-500 mg bid
PO: 250-500 mg tid-qid
IV: 500 mg-1 g qid
PO: 800 mg daily
Elimination
Hepatic/biliary
Hepatic/renal*
Hepatic/biliary
Biliary/hepatic/
renal*
bid, twice daily; qid, 4 times daily; tid, 3 times daily

*Adjust dose for renal function.
Azithromycin and clarithromycin have enhanced activity

over erythromycin against H. influenzae and several
nontubercular mycobacterial species.
Telithromycin has enhanced activity for S. pneumoniae
(including strains resistant to macrolides); it retains activity
against H. influenzae, M. catarrhalis, Mycoplasma,
Legionella, and C. pneumoniae
Toxicities
GI side effects (more common with erythromycin and
telithromycin), diplopia (telithromycin), rare reversible hearing loss with high doses
Can prolong the QT interval, with rare reports of torsades de
pointes; this may be least significant for azithromycin.
Agents except azithromycin inhibit metabolism of other
drugs through the cytochrome P-450 (CYP) 3A4 system;
the potential for drug interactions should be reviewed
closely.
Trimethoprim-Sulfamethoxazole (Table 9)
Includes a wide variety of aerobic gram-positive cocci and
gram-negative bacilli: staphylococci (moderate activity),
most S. pneumoniae, H. influenzae, M. catarrhalis, L. monocytogenes, and many Enterobacteriaceae.
775
Table 9. Miscellaneous Antibacterials
Drug
Clindamycin
Daptomycin
Linezolid
Metronidazole
Dalfopristinquinupristin
Trimethoprimsulfamethoxazole
Usual adult dose

for normal
renal function
Elimination
PO: 150-450 mg qid

IV: 300-900 mg q 6-8 hours
4 mg/kg IV daily (6 mg/kg
under study)
600 mg bid (PO or IV)
7.5 mg/kg (500 mg) q
6-12 hours
7.5 mg/kg IV q 8-12 hours
Hepatic
PO: 1 DS bid
IV: 8-15 mg/kg daily in
3-4 divided doses
Renal*
Renal*
Hepatic
Hepatic
Hepatic
bid, twice daily; DS, double strength; q, every; qid, 4 times daily.
Active against Pneumocystis, Stenotrophomonas, Nocardia,

Shigella, and Isospora, but not Pseudomonas
Toxicities
Hypersensitivity reactions and GI side effects are most common.
Nephrotoxicity, myelosuppression, and hyperkalemia are less
frequent but may occur, especially with high-dose therapy.
Use with caution or avoid during the last trimester of pregnancy (to minimize risk of fetal kernicterus) and in patients
with known glucose-6-phosphatase dehydrogenase deficiency.
Clindamycin (Table 9)
Includes aerobic and anaerobic gram-positive organisms.
Its anaerobic activity includes Actinomyces spp, Clostridium
(except C. difficile), Peptostreptococcus and most Bacteroides
spp, but, 10%-20% of B. fragilis organisms are resistant.
Clindamycin is active against gram-positive aerobes such
as many staphylococci and group A streptococci, but
emergence of resistance by staphylococci can occur during
treatment.
776
IV THERAPY
Toxicities
Most commonly include rash and GI side effects
Antibiotic-associated diarrhea can occur in up to 20% of
patients, and C. difficile colitis occurs in 1%-10%.
Metronidazole (Table 9)
Includes most anaerobic microorganisms, including
Bacteroides spp.
Exceptions include some anaerobic gram-positive organisms:
Peptostreptococcus, Actinomyces, and Propionibacterium
acnes.
Also effective against Entamoeba histolytica, Giardia, and
Gardnerella.
Toxicities
Include nausea, vomiting, reversible neutropenia, metallic
taste, and a disulfiram reaction when coadministered with
alcohol.
Dalfopristin-quinupristin (Synercid) (Table 9)
Good activity against gram-positive cocci, including vancomycin-resistant Enterococcus faecium and staphylococcus, including methicillin-resistant strains, but, activity against
E. faecalis is substantially decreased.
Toxicities
A relatively high rate of inflammation and irritation at the
infusion site, arthralgias, myalgias, and hyperbilirubinemia
Can inhibit the metabolism of other drugs metabolized via the
CYP 3A4 enzyme system and close attention should be paid
to possible drug interactions.
Linezolid (Table 9)
Has activity against gram-positive bacteria, including methicillin-resistant staphylococci, most vancomycin-resistant
enterococci, and penicillin-resistant S. pneumoniae
777
Also has activity against Nocardia and some mycobacterial

species
Toxicities
The most prominent is myelosuppression, especially with
prolonged use
Headache, diarrhea, and peripheral or optic neuropathy also
can occur.
Linezolid is a weak monoamine oxidase inhibitor that can
interact with some medications, such as selective serotonin
reuptake inhibitors and monoamine oxidase inhibitors.
Daptomycin (Table 9)
Includes Staphylococcus (including methicillin-resistant
strains), Streptococcus pyogenes, S. agalactiae, and
Enterococcus (including vancomycin-resistant strains)
Toxicities
GI effects, hypersensitivity reactions, headache, insomnia,
myalgias, and CK elevations.
Manufacturer suggests stopping statins during daptomycin
therapy and monitoring CK values weekly.
ANTIVIRAL AGENTS
AntiHerpes Simplex Virus (HSV) Agents (Table 10)
Agents
Acyclovir, valacyclovir, famciclovir
Acyclovir and its prodrug, valacyclovir, have clinical activity against HSV-1 and HSV-2, are also active against
varicella-zoster virus (VZV), but are not effective against
cytomegalovirus (CMV).
Famciclovir is active against HSV-1, HSV-2, and VZV.
Toxicities
Acyclovir has been associated with neurotoxicity, nephrotoxicity (IV), and GI effects.
Patients on high-dose IV acyclovir should be well hydrated
to minimize drug precipitation in renal tubules.
778
IV THERAPY
Table 10. Anti-HSV Agents
Drug
Acyclovir
Valacyclovir
Famiciclovir
Usual adult dose

for normal
renal function
Elimination
Mucocutaneous disease: 5 mg/kg

Renal*
IV q 8 hours
HSV encephalitis: 10 mg/kg
IV q 8 hours
Varicella-zoster (immunocompromised): 10-12 mg/kg IV q 8 hours
Genital herpes: 400 mg PO tid or
800 mg PO bid
Varicella-zoster: 600-800 mg PO
5 per or 1,000 mg PO q 6 hours
Chronic suppression for recurrent
infection: 400 mg PO bid
(400 mg-800 mg PO bid-tid in
HIV)
Herpes zoster: 1 g PO tid
Renal*
First episode genital herpes:
1 g PO bid
Recurrent genital herpes:
500 mg PO bid
Suppression for recurrent genital
herpes: 500-1,000 mg PO daily
Herpes zoster: 500 mg q 8 hours
Renal*
Recurrent genital herpes in HIV
patients: 500 mg bid
Recurrent genital herpes (nonHIV): 125 mg bid
Suppression of recurrent genital
herpes: 250 mg bid
bid, twice daily; HSV, herpes simples virus; q, every; tid, 3 times daily.
779
Famciclovir is associated with headache, nausea, diarrhea,

and rare CNS effects, specifically confusion or hallucinations;
neutropenia and liver function test elevations may occur rarely.
Anti-Cytomegalovirus Agents (Table 11)

Agents
Ganciclovir, valganciclovir, cidofovir, foscarnet
Ganciclovir and its prodrug, valganciclovir, are clinically
active against CMV, HSV-1 and HSV-2, VZV, and human
herpesvirus (HHV)-6.
Cidofovir and foscarnet are clinically active against CMV
(including many ganciclovir-resistant strains), HSV-1 and
HSV-2 (including many acyclovir-resistant strains), VZV,
and HHV-6.
Toxicities
Ganciclovir and valganciclovir are associated with myelosuppression, generally neutropenia or thrombocytopenia.
Less commonly, nephrotoxicity, liver function test elevations, and fever can occur.
CNS effects, including headache, confusion, seizures, and
coma, have been described but are rare.
Cidofovir can cause dose-related nephrotoxicity, neutropenia,
iritis, uveitis, and GI effects.
Saline hydration and probenecid should be used to decrease
the risk of nephrotoxicity.
Foscarnet is associated with nephrotoxicity, electrolyte
disturbances, and CNS effects; fever, nausea, vomiting, and
diarrhea are common.
Anti-Influenza Agents (Table 12)

Agents
Rimantadine, amantadine, oseltamivir, zanamivir
Rimantadine and amantadine are active only against influenza
A; resistance is increasing.
Oseltamivir and zanamivir are active against influenza A
and B and have activity against avian influenza.
780
IV THERAPY
Table 11. Anti-Cytomegalovirus Agents
Drug
Usual adult dose

for normal
renal function
Ganciclovir
IV induction: 5 mg/kg q 12 hours

IV maintenance: 5 mg/kg q 24
hours
PO: 1 g tid
Valganciclovir Induction: 900 mg PO bid
Maintenance: 900 mg PO daily
Cidofovir
Induction: 5 mg/kg IV weekly
2 weeks
Maintenance: 5 mg/kg IV every
other week
Foscarnet
Induction: 60 mg/kg (over 1 hour)
IV q 8 hours or 90 mg/kg (over
1-2 hours) IV q 12 hours 14-21
days
Maintenance: 90-120 mg/kg
(over 2 hours) IV q 24 hours
Elimination
Renal*
Renal*
Renal*
Renal*
bid, twice daily; q, every; tid, 3 times daily.

Toxicities
Rimantadine and amantadine
Commonly associated with GI complaints and CNS effects,
including insomnia, anxiety, difficulty concentrating.
Neurotoxicity, including tremor, seizures, and coma, has
been reported at high doses and doses unadjusted for renal
function.
CNS effects are less pronounced with rimantadine.
Dose-related cardiac arrhythmias have been reported rarely.
Zanamivir and oseltamivir
Generally well tolerated, with GI complaints most
frequently reported
Zanamivir may rarely cause cough and bronchospasm and
781
Table 12. Anti-Influenza Agents
Drug
Amantadine
Rimantadine
Oseltamivir
Zanamivir
Usual adult dose

for normal
renal function
Treatment or prophylaxis: 100
mg PO bid (or 100 mg PO
daily for patients 65 years)
5 days
Treatment or prophylaxis: 100
mg PO bid (or 100 mg PO
daily for patients 65 years)
5 days
Treatment: 75 mg PO bid
5 days
Prophylaxis: 75 mg PO daily
Treatment: 10 mg (2 inhalations)
bid 5 days
Elimination
Renal*
Hepatic/renal*
Hepatic/renal*
Renal
bid, twice daily.

is not recommended in patients with underlying chronic

pulmonary disease.
Antihepatitis Agents (see Appendix 2)
Antiretroviral Agents
Prototypic Agents
Nucleoside/nucleotide reverse transcriptase inhibitors
Abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, zalcitabine, zidovudine
Combination agentsCombivir (zidovudine-lamivudine),
Trizivir (zidovudine, lamivudine, abacavir), Epzicom (abacavir-lamivudine), Truvada (tenofovir-emtricitabine)
Non-nucleoside reverse transcriptase inhibitorsefavirenz,
nevirapine, delavirdine
Protease inhibitorsamprenavir, atazanavir, fosamprenavir, indinavir, lopinavir-ritonavir, nelfinavir, ritonavir,
saquinavir, tipranavir
Fusion inhibitorenfuvirtide
782
IV THERAPY
Novel Adverse Effects
Nucleoside/nucleotide reverse transcriptase inhibitorsclass
side effects include rare lactic acidosis, hepatic steatosis and
lipoatrophy; more common with stavudine and didanosine,
especially in combination.
Abacavir has potential for serious hypersensitivity
reactions; symptoms may include fever, rash, GI (nausea,
vomiting, diarrhea, or abdominal pain), constitutional
(generalized malaise, fatigue, or achiness), and respiratory
(dyspnea, cough, or pharyngitis).
Avoid abacavir rechallenge in patients with suspected
or confirmed hypersensitivity because severe and even
fatal reactions can occur.
Didanosine, zalcitabine, and stavudine can cause peripheral neuropathy.
Didanosine is associated with pancreatitis.
Zidovudine can cause myelosuppression, especially in
combination with other myelosuppressive drugs.
Tenofovir has been anecdotally reported to cause renal toxicity (proximal tubular dysfunction and Fanconi syndrome).
Non-nucleoside reverse transcriptase inhibitorsclass side
effects include hypersensitivity reactions and hepatotoxicity
All can cause hepatotoxicity, especially with underlying
liver disease; incidence is highest with nevirapine in women
with CD4 250 cells/mm3 or men with CD4 400 cells/mm3.
Efavirenz can cause CNS effects such as insomnia, vivid
dreams, trouble concentrating, and hallucinations; these
often resolve after first 2-4 weeks.
Drug interactions should be reviewed closely because
non-nucleoside reverse transcriptase inhibitors can induce
metabolism of other drugs via the cytochrome P-450
system (efavirenz is a mixed inducer-inhibitor).
Protease inhibitorsclass side effects include hyperlipidemia
(especially triglycerides), glucose intolerance, and lipodystrophy (these may be less common with atazanavir); more
rarely, spontaneous bleeding has been noted in hemophiliacs.
GI side effects appear most frequent with lopinavir-ritonavir, high-dose ritonavir, and nelfinavir.
783
Nephrolithiasis can occur with indinavir; patients should

stay well hydrated to minimize this.
Atazanavir can cause hyperbilirubinemia (usually asymptomatic)
Drug interactions should be reviewed closelymost
commonly, protease inhibitors inhibit metabolism of other
drugs via CYP 3A4, and some can also be inducers of
other CYP isoenzymes.
Fusion inhibitor (enfuvirtide)local site reactions with SQ
injection are common.
For drug selection and drug dosing, see the latest guidelines
from the U.S. Department of Health and Human Services:
http://aidsinfo.nih.gov/guidelines/.
ANTIFUNGAL AGENTS
Azoles
Agents
Fluconazole, itraconazole, voriconazole, posaconazole (under
review by U.S. Food and Drug Administration) (Table 13)
Fluconazoleactive against most Candida spp (less activity against C. glabrata, inactive against C. krusei),
Cryptococcus, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, and Paracoccidioides sp
Itraconazole
Active against some filamentous fungi, including
Aspergillus spp, Pseudallescheria sp, Alternaria sp, etc.
Similar activity against most yeasts as fluconazole but
with greater activity against Histoplasma and Blastomyces
infections and active against most fluconazole-resistant
Candida spp (but cross-resistance can occur)
Voriconazoleactive against many filamentous fungi including Aspergillus spp, Pseudallescheria/Scedosporium sp,
Fusarium spp, while retaining similar anti-Candida activity as fluconazole and itraconazole (may be active against
fluconazole and itraconazole-resistant strains, but crossresistance can occur)
Posaconazoleactivity similar to voriconazole but possesses
some activity against the Zygomycetes.
784
IV THERAPY
Table 13. Azole Antifungal Dosing
Drug
Fluconazole
(PO/IV)
Itraconazole PO
Itraconazole IV
Voriconazole PO
Voriconazole IV
Posaconazole
(PO only)
Usual adult dose

for normal
renal function
Excretion
(liver/kidney)
200-400 mg daily
Renal*
200 mg daily-bid
200 mg daily
200-300 mg bid
6 mg/kg q 12 hours 2 days,
then 4 mg/kg q 12 hours
400 mg bid or 200 mg qid
Hepatic
Hepatic
Hepatic
Hepatic
Hepatic
bid, twice daily; q, every; qid, 4 times daily.

*Adjust doses for renal function.
Itraconazole capsules require gastric acid (low pH) for adequate absorption,
but liquid PO itraconazole does not have this requirement.
After loading dose of 200 mg IV every 12 hours 2 days.
Currently under review by U.S. Food and Drug Administration.
Toxicities
All azoles can cause elevated liver function tests and, less
commonly, hepatotoxicity.
Itraconazole and voriconazole inhibit liver metabolism (and
secondarily increase serum drug concentrations of many drugs,
including cyclosporine, tacrolimus, digoxin, midazolam, and
triazolam; review potential drug interactions closely).
About 10% of patients starting voriconazole develop transient
visual disturbances.
Rash is more common with voriconazole.
Itraconazole IV and voriconazole IV contain a cyclodextrin
vehicle that can accumulate with renal dysfunction; clinical
significance is unclear; use with caution in patients with
renal dysfunction (assess risk/benefit).
Polyenes: Amphotericin B Products
Agents
Amphotericin B deoxycholate and lipid formulations of
amphotericin (AmBisome, Abelcet, Amphotec) (Table 14)
785
Table 14. Amphotericin Dosing*

Drug
Usual adult dose
Amphotericin B
deoxycholate
AmBisome
0.25-1.5 mg/kg daily

3-5 mg/kg daily
Abelcet
3-5 mg/kg daily
Amphotec
3-5 mg/kg daily
Excretion
(liver/kidney)
Intracellular degradation
*Doses may be increased for invasive molds.

Doses 5-10 mg/kg often used for treatment of Zygomycetes and other
refractory invasive molds.
Broadest antifungal activity, including yeasts (Candida
spp, Cryptococcus, etc.), dimorphic fungi (Histoplasma,
Coccidioides, Blastomyces), and filamentous fungi
(Aspergillus, the Zygomycetes and dematiaceous molds).
Toxicities
Infusion-related: fever, chills, rigors, nausea, vomiting
Pretreatment with diphenhydramine, acetaminophen,
meperidine may lessen these reactions.
These are less frequent with AmBisome.
Nephrotoxicity (usually reversible)can be lessened by
sodium crystalloid loading
Others: hypokalemia, hypomagnesemia, anemia, phlebitis,
changes in blood pressure, neurologic effects
Lipid amphotericin agents have less nephrotoxicity than
amphotericin B deoxycholate.
Echinocandins
Agents
Caspofungin, micafungin, anidulafungin (investigational)
(Table 15)
Active against Candida spp (including azole-resistant strains)
and Aspergillus spp
786
IV THERAPY
Not active against Cryptococcus spp and the Zygomycetes
Toxicities (Not Common)

Possible histamine-related effectsrash, facial swelling
Liver function test abnormalities
ANTIMYCOBACTERIAL AGENTS
Anti-TB Agents
First-Line Agents
Isoniazid, a rifamycin (rifampin, rifabutin, rifapentine), pyrazinamide, ethambutol (Table 16)
Toxicities
Isoniazidhepatitis, peripheral neuropathy, rash and other
skin eruptions, rarely seizures.
Rifampinhepatitis (may show cholestatic pattern), orange
discoloration of urine and tears (not a toxicity), rash and
other skin eruptions, thrombocytopenia, anemia, flulike
symptoms, nephritis, proteinuria
Rifampin induces hepatic CYP P-45 metabolic pathway, resulting in decreased serum concentrations of
concomitantly administered drugs metabolized by this
same pathway, including the following: azathioprine,
azole antifungals, calcium channel blockers, corticosteroids, cyclosporine, dapsone, diazepam, digoxin,
haloperidol, imidazoles, opioids/methadone, oral
contraceptives, oral hypoglycemic agents, phenytoin,
propranolol, protease inhibitors, quinidine, theophylline,
tolbutamide, warfarin.
Rifabutin
Profile similar to rifampin plus uveitis, arthritis and
arthralgias, neutropenia and leukopenia, bronze skin
pigmentation.
Less hepatic CYP P-450 induction than rifampin
Pyrazinamidehepatitis, arthralgias, hyperuricemia (not a
toxicity), rash
Ethambutoloptic neuritis (decreased visual acuity or redgreen color discrimination)
787
Table 15. Echinocandins

Drug
Caspofungin
Micafungin
Anidulafungin
Usual adult dose

70 mg IV load 1, then 50 mg
IV daily
50-150 mg daily
Investigational
Excretion
(liver/kidney)
Hepatic
Hepatic
Investigational
Table 16. Dosing of Anti-TB Drugs (Adult Dosing)

Drug
Isoniazid
Rifampin
Rifabutin
Rifapentine
Pyrazinamide,
patient weight
Usual adult dose

300 mg daily
900 mg 2 or 3 times weekly
600 mg daily
300 mg daily
600 mg once weekly
Hepatic
Hepatic
Hepatic
Hepatic
Daily
Twice
weekly
3 times
weekly
40-55 kg
56-75 kg
76-90 kg
Ethambutol,
patient weight
1,000 mg 1,500 mg 2,000 mg

1,500 mg 2,500 mg 3,000 mg
2,000 mg 3,000 mg 4,000 mg
40-55 kg
56-75 kg
76-90 kg
800 mg 1,200 mg 2,000 mg

1,200 mg 2,000 mg 2,800 mg
1,600 mg 2,400 mg 4,000 mg
Hepatic
Daily
788
Excretion
(liver/kidney)
Twice
weekly
3 times
weekly
IV THERAPY
Second-Line Agents
Fluoroquinolones (moxifloxacin, levofloxacin), aminoglycosides (streptomycin, amikacin, kanamycin), capreomycin,
ethionamide, cycloserine, para-aminosalicylic acid, linezolid, clofazimine
Non-TB Mycobacteria Agents
Selection of drugs depends on specific mycobacteria species
but may include macrolides (clarithromycin, azithromycin),
fluoroquinolones (moxifloxacin, levofloxacin, ciprofloxacin),
doxycycline, tigecycline, trimethoprim-sulfamethoxazole,
amikacin, tobramycin, imipenem, linezolid, cefoxitin, clofazimine.
Acknowledgment: The authors acknowledge the specific contributions

of Glenn D. Roberts, Ph.D., and Rachel M. Chambers, Pharm.D.
789
Appendix 1. Organism Taxonomy

Aerobic Bacteria
Gram-positive cocci
Staphylococcus spp
S. aureus
S. epidermidis
S. saprophyticus
S. lugdunensis
Other Staphylococcus spp
Streptococcus spp
S. pyogenes (group A)
S. agalactiae (group B)
Streptococcus groups C, F, G
S. pneumoniae
S. bovis
Viridans group streptococci
S. anginosus
S. constellatus
S. criceti
S. crista
S. downei
S. gordonii
S. infantis
S. intermedius
S. macacae
S. mitis
S. mutans
S. oralis
S. parasanguinis
S. peroris
S. rattus
S. salivarus
S. sanguis
S. sobrinus
S. thermophilus
S. vestibularis
Enterococcus spp
E. faecalis
E. faecium
Rhodococcus equi
Micrococcus spp
Gram-positive bacilli
Bacillus anthracis
Bacillus cereus
Corynebacterium diphtheriae
Corynebacterium jeikeium
Corynebacterium spp (other)
Erysipelothrix rhusiopathiae
790
Gram-negative cocci
Neisseria gonorrhoeae
Neisseria meningitidis
Moraxella (Branhamella)
catarrhalis
Gram-negative bacilli
Enterobacteriaceae
Escherichia coli
Klebsiella pneumoniae
Enterobacter spp
Citrobacter spp
Proteus mirabilis (indolenegative)
Proteus vulgaris (indolepositive)
Morganella morganii
Serratia spp
Salmonella spp
Shigella
Providencia spp
Yersinia spp
Edwardsiella spp
Hafnia spp
Acinetobacter spp
Stenotrophomonas maltophilia
Pseudomonas aeruginosa
Pseudomonas spp (other)
Aeromonas hydrophila
Moraxella spp
Alcaligenes spp
Flavobacterium spp
Haemophilus spp
Bartonella spp
Bordetella spp
Brucella spp
Burkholderia cepacia
Calymmatobacterium
granulomatis
Capnocytophaga spp
Francisella tularensis
Gardnerella vaginalis
HACEK group: Haemophilus
parainfluenzae, H. aphrophilus,
H. paraphrophilus, Actinobacillus actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens,
Kingella kingae
Legionella spp
Providencia spp
Vibrio spp
IV THERAPY
Appendix 1 (continued)
Anaerobic Bacteria
Gram-positive cocci
Peptostreptococcus spp
Gram-positive bacilli
Actinomyces spp
Bifidobacterium spp
Clostridium botulinum
Clostridium perfringens
Clostridium tetani
Eubacterium spp
Lactobacillus spp
Leptotrichia spp
Gram-positive bacilli (continued)

Mobiluncus spp
Propionibacterium spp
Rothia spp
Gram-negative cocci
Veillonella spp
Gram-negative bacilli
Bacteroides spp
Fusobacterium spp
Porphyromonas spp
Prevotella spp
Fungi*
Yeastsgrow as single cells and
reproduce by budding
Candida spp
C. albicans
C. tropicalis
C. parapsilosis
C. glabrata
C. krusei
C. lusitaniae
C. guilliermondii
Cryptococcus neoformans
Other Cryptococcus spp
Blastoschizomyces capitatus
(formerly called Trichosporon
capitatum)
Malassezia spp
Malassezia furfur
Saccharomyces cerevisiae
Rhodotorula spp
Trichosporon spp includes
T. cutaneum, asteroides,
ovoides, inkin, asahii, mucoides
Dimorphic fungiexhibit two

different growth forms: outside
the body, they grow as a mold,
producing hyphae and asexual
reproductive spores; in the body,
they grow in a non-mycelial form
Dimorphic fungi (continued)

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Paracoccidioides brasiliensis
Sporothrix schenckii
Penicillium marneffei
Dermatophytessuperficial
skin/hair infections
Epidermophyton spp
Microsporum spp
Trichophyton spp
Filamentous fungireproduce
principally by elongation at tips of
filamentous growth forms
Hyaline hypomycetescolorless fungi

Aspergillus spp includes (list
not complete) A. flavus, niger,
clavatus, terreus, fumigatus,
glaucus group, nidulans,
oryzae, ustus, versicolor
Acremonium spp
Chrysosporium spp
Fusarium spp
Geotrichum spp
791
Hyaline hypomycetes (continued)
Paecilomyces spp
Penicillium spp
Scedosporium apiospermum
(Pseudallescheria boydii is
sexual form)
Scopulariopsis spp (sexual form
is Microascsus)
Trichoderma spp
Verticillium spp
Zygomycetes (aseptate or few
septates) includes Absidia,
Apophysomyces, Basidiobolus,
Conidiobolus, Cokeromyces,
Cunninghamella, Mortierella,
Mucor, Rhizomucor, Rhizopus,
Saksenaea vasiformis,
Syncephalastrum
Dematiaceous Hyphomycetes
produce dark brown or black
melanin pigment in cell walls
(phaeohyphomycosis)
Alternaria spp
Aureobasidium spp
Bipolaris spp
Chaetomium spp
Cladophialophora spp
Cladosporium spp
Curvularia spp
Ochroconis (Dactylaria) spp
Drechslera spp
Epicoccum spp
Exophiala jeanselmei
Fonsecaea spp
Lecythophora spp
Hortaea werneckii
Phialophora spp
Ramichloridium spp
Scedosporium prolificans
Ulocladium spp
Wangiella dermatidis
*Clinical and histologic groupings; not all human pathogenic fungi listed.
Viruses
DNA viruses
Pox virus group
Vaccina virus (cowpox)
Variola (smallpox)
Parapoxvirus (milkers nodule)
Molluscum contagiosum
Herpesvirus group
Herpes simplex virus (HSV)
1&2
Varicella-zoster virus (VZV)
Cytomegalovirus (CMV)
Epstein-Barr virus (EBV)
Human herpesvirus 6 & 7
Human herpesvirus 8 (Kaposi
sarcoma)
Herpes B virus
Adenovirus
Human papillomavirus (HPV)
Polyomavirus group
JC virus
BK virus
Hepatitis B virus (HBV)
Parvoviruses (B19 virus)
792
RNA viruses
Enterovirus group
Poliovirus
Coxsackieviruses A & B
Echovirus
Enterovirus
Rhinovirus
Hepatitis A virus (HAV)
Influenza virus (A, B, C)
Paramyxovirus group
Parainfluenza virus
Mumps virus
Measles virus (rubeola)
Respiratory syncytial virus
(RSV)
Rabies virus
Arbovirus group
Alphavirus group
Eastern equine encephalitis
(EEE) virus
Western equine encephalitis (WEE) virus
Venezuelan equine encephalitis (VEE) virus
IV THERAPY
RNA viruses (continued)
Chikungunya virus
Onyong-nyong virus
Flavivirus group
Yellow fever virus
Dengue fever virus
St. Louis encephalitis
virus
Japanese encephalitis
virus
West Nile virus
Powassan encephalitis
virus
Murray Valley encephalitis
virus
Hepatitis C virus (HCV)
Rubella virus (German
measles)
La Crosse encephalitis virus
Hantavirus
Retrovirus group
HIV 1 & 2
Human T-cell lymphotropic
virus 1 & 2
Lymphocytic choriomeningitis
(LCM) virus
Lassa virus (Lassa fever)
Calicivirus
Norwalk & Norwalk-like viruses
Astrovirus
Colorado tick fever virus (an
arbovirus)
Ebola virus
Marburg virus
Coronavirus
Rotavirus
Hepatitis E virus
Appendix 2. Treatment of Specific Organisms

Information provided is not intended to replace clinical judgment.
Patients conditions may vary and require adjustments in therapy.
An infectious disease consultation should be considered to assist
in patient care.
Bacterial Organism-Specific Treatment
Organism
Preferred therapy
Acinetobacter
Meropenem,
imipenem (not
ertapenem)
Actinomyces
Penicillin
Aeromonas
tmp-smx, quinolone
Alternative agents
(depending on
susceptibility)
Tigecycline, piperacillintazobactam, ceftazidime,
cefepime, quinolone,
aminoglycoside, colistin,
minocycline, tmp-smx
Ampicillin-amoxicillin,
doxycycline, cephalosporin, clindamycin,
erythromycin
Carbapenem,* gentamicin,
3rd-generation cephalosporin
793
Organism
Bacillus
anthracis
(anthrax)
Bacillus spp
Preferred therapy
Ciprofloxacin,
doxycycline
Amoxicillin, penicillin,
levofloxacin, imipenem
Vancomycin
Clindamycin, carbapenem,* quinolone

Carbapenem,* -lactam/
-lactamase inhibitor,
clindamycin, moxifloxacin, cefotetan, cefoxitin
Bacteroides
fragilis
Metronidazole
Bartonella
henselae &
B. quintana
Bordetella
pertussis
Borrelia
burgdorferi
(Lyme disease)
Macrolide,
doxycycline
Brucella spp
Doxycycline plus
gentamicin or
streptomycin or
rifampin
Often a colonizer,
tmp-smx
Erythromycin,
azithromycin
Clindamycin,
amoxicillinclavulanate
Burkholderia
cepacae
Campylobacter
jejuni
Capnocytophaga spp
Macrolide
Tmp-smx
Doxycycline,
amoxicillin
Penicillin, cefuroxime
axetil, cefotaxime,
ceftriaxone, azithromycin, clarithromycin
Tmp-smx, ciprofloxacin,
chloramphenicol; each
gentamicin/streptomycin or rifampin
Ceftazidime, cefepime,
carbapanem,* quinolone
Doxycycline, quinolone,
gentamicin, furazolidone
Erythromycin, quinolone,
carbapenem,* doxycycline, -lactam/lactamase inhibitor
Quinolone, telithromycin
Chlamydia
pneumoniae
Citrobacter
freundii
Doxycycline,
macrolide
Carbapenem*
Clostridium
difficile
Metronidazole
794
Alternative agents
(depending on
susceptibility)
Quinolone, aminoglycoside, tmp-smx, 3rd or

4th-generation cephalosporin, piperacillintazobactam
Vancomycin (PO)
IV THERAPY
Organism
Preferred therapy
Clostridium
perfringens
Penicillin
Clostridium
tetani
Metronidazole +
tetanus immune
globulin & tetanus
toxoid
Erythromycin +
antitoxin
Vancomycin
Corynebacterium diptheriae
Corynebacterium JK group
Coxiella
burnetti (Q
fever)
Ehrlichia
Eikenella
corrodens
Enterobacter
Alternative agents
(depending on
susceptibility)
Metronidazole, clindamycin, -lactam/-lactamase
inhibitor, carbapenem*
Doxycycline, penicillin
Clindamycin, penicillin
Penicillin + gentamicin,
macrolide
Acute: doxycycline Acute: quinolone, macroChronic (endocarlide
ditis): doxycycline Chronic: doxycycline +
+ hydroxychloroquinolone, doxycycline +
quine; doxycycline
rifampin
+ quinolone
Doxycycline
Ampicillin-amoxicil- Doxycycline, -lactam/
lin, 3rd generation
cephalosporin
quinolone
Carbapenem*
Quinolone, tmp-smx,
cefepime, piperacillintazobactam, aminoglycoside
Enterococcus
spp
Ampicillinsensitive
Ampicillin-amoxicil- Vancomycin, -lactam/

lin, penicillin
linezolid, dalfopristinquinupristin (E. faecium
only), tigecycline
Ampicillin- Vancomycin
Linezolid, daptomycin,//
resistant,
dalfopristin-quinupristin
vancomy(E. faecium only),
cin-sensitive
tigecycline
Vancomycin- Linezolid
Daptomycin,// dalfoprisresistant
tin-quinupristin (E.
faecium only), tigecycline
795
Organism
Erysipelothrix
rhusiopathiae
Escherichia
coli
Francisella
tularensis
(tularemia)
Fusobacterium
Gardnerella
vaginalis
(bacterial
vaginosis)
Haemophilus
influenzae
Preferred therapy
Alternative agents
(depending on
susceptibility)
Penicillin
Cephalosporin, quinolone,
clindamycin, carbapenem*
Ceftriaxone, cefoQuinolone, aminoglycotaxime, cefepime
side, other cephalosporin,
(use a carbapenem* -lactam/-lactamase
for ESBL-producinhibitor, ampicillin,
ing strains)
tmp-smx
Streptomycin,
gentamicin (both
chloramphenicol
+ doxycycline or
chloramphenicol
for CNS infections)
Penicillin
Metronidazole, clindamycin, -lactam/-lactamase
inhibitor, carbapenem*
Metronidazole
Topical metronidazole,
topical or PO clindamycin
Quinolone, tmp-smx,
azithromycin, clarithromycin, telithromycin,
-lactam/-lactamase
inhibitor, doxycycline
Klebsiella
Ceftriaxone, cefoQuinolone, aminoglycopneumoniae
taxime, cefepime
side, tmp-smx, -lactam/
(use a carbapenem* -lactamase inhibitor,
for ESBL-produccarbapenem*
ing strains)
Leuconostoc spp Ampicillin/amoxicil- Clindamycin, doxycycline,
lin, penicillin
macrolide
Legionella spp Newer quinolone,
Other macrolide, doxyazithromycin
cycline, tmp-smx; each
rifampin
rifampin
Listeria mono- Ampicillin or peni- Tmp-smx
cytogenes
cillin gentamicin
Moraxella
2nd or 3rd-generaQuinolone, azithromycin,
catarrhalis
tion cephalosporin
clarithromycin, telithromycin, tmp-smx, cefepime, doxycycline, lactam/-lactamase
inhibitor
796
Ceftriaxone,
cefotaxime
IV THERAPY
Organism
Morganella
morganii
Mycobacterium
aviumintracellulare
Mycobacterium
chelonae
Mycobacterium
abscessus
Mycobacterium
fortuitum
Preferred therapy
3rd or 4th-generation
cephalosporin,
quinolone
Treatment: clarithromycin + ethambutol
rifabutin or
rifampin
Prophylaxis:
azithromycin,
clarithromycin
Tobramycin +
imipenem +
clarithromycin;
Localized skin infection: clarithromycin
Amikacin + cefoxitin
+ clarithromycin or
imipenem
Imipenem or cefoxitin
+ amikacin
Mycobacterium Isoniazid + rifampin

kansasii
ethambutol or
streptomycin
Mycobacterium Dapsone + rifampin
leprae
clofazimine
Mycobacterium Clarithromycin, tmpmarinum
smx, minocycline,
or rifampin +
ethambutol
Mycobacterium 4-drug combo:
tuberculosis
isoniazid, rifampin,
ethambutol, pyrazinamide
Alternative agents
(depending on
susceptibility)
tmp-smx, carbapenem,*
piperacillin-tazobactam,
aminoglycoside
As parts of combination
treatment: newer quinolone, amikacin
Amikacin, newer quinolones, azithromycin,

linezolid
Newer quinolones,
azithromycin, linezolid
Newer quinolones,
clarithromycin, sulfamethoxazole, doxycycline, linezolid
Clarithromycin, azithromycin, ethionamide,
cycloserine, rifabutin,
quinolone
Minocycline, clarithromycin, quinolone
As parts of combination
treatment: newer quinolones, cycloserine, capreomycin, amikacin,
kanamycin, ethionamide,
para-aminosalicyclic
acid, linezolid
797
Organism
Mycoplasma
pneumoniae
Neisseria
gonorrhoeae
Neisseria
meningitidis
Nocardia
asteroides
Preferred therapy
Macrolide
Alternative agents
(depending on
susceptibility)
telithromycin
Ceftriaxone,
Cefotaxime, quinolone
cefixime
(variable resistance)
Penicillin, ceftriAmpicilln, quinolone,
axone, cefotaxime
tmp-smx
Tmp-smx
Minocycline, imipenem
amikacin, sulfonamide,
ceftriaxone amikacin,
amoxicillin-clavulanate,
linezolid
Pasteurella
Penicillin, ampicillin, Doxycycline, 2nd/3rdmultocida
amoxicillin
generation cephalosporin,
tmp-smx, -lactam/lactamase inhibitor,
carbapenem
PeptostreptoPenicillin, ampicillin, Clindamycin, cephalococcus
amoxicillin
sporin, newer quinolone,
carbapenem,* vancomycin, telithromycin, lactam/-lactamase
inhibitor
Propionibacter- (Common blood
Clindamycin, doxycycline,
ium acnes
culture contaminant) carbapenem*
(systemic
Penicillin
infection)
Proteus
Ampicillin, amoxiCephalosporin, quinolone,
mirabilis
cillin
aminoglycoside, tmpsmx, -lactam/lactamase inhibitor,
carbapenem*
Proteus vulgaris 3rd or 4th-generation Quinolone, aminoglycoand Provicephalosporin,
side, tmp-smx,
dencia
carbapenem*
piperacillin-tazobactam
Pseudomonas
Cefepime, ceftaziCiprofloxacin,
aeruginosa
dime, meropenem
piperacillin-tazobactam,
or imipenem (not
colistin, aztreonam
ertapenem); consider
addition of aminoglycoside or ciprofloxacin for severe
infection or until
susceptibilities
available
798
IV THERAPY
Organism
Rickettsia spp
Salmonella spp
Serratia
Shigella
Preferred therapy
Doxycycline
Quinolone, chloramphenicol
Treatment not indi- Amoxicillin or ampicillin,
cated for uncompli- chloramphenicol, tmpcated disease;
smx, other 3rd/4thquinolone, ceftrigeneration cephalosporin
axone
Carbapenem*
Quinolone, aminoglycoside, 3rd/4th-generation
cephalosporin, tmp-smx,
piperacillin-tazobactam
Quinolone
tmp-smx, 3rd/4thgeneration cephalosporin,
azithromycin
Staphylococcus#
PenicillinPenicillin
sensitive
(rare)
Oxacillin/
Nafcillin, oxacillin,
methicillin- cefazolin
sensitive
staphylococci
Oxacillinresistant
staphylococci
(MRSA,
MRSE)
Alternative agents
(depending on
susceptibility)
Vancomycin,
linezolid
Any agent below in either

column
1st-generation cephalosporins, clindamycin,
tmp-smx, minocycline
Broad spectrum agents
that have coverage for
oxacillin-sensitive
staphylococci: cefepime,
-lactam/-lactamase
inhibitor, carbapenem,*
newer quinolone
Daptomycin, tigecycline,
Depending on susceptibility for mild-moderate
infections or step-down
therapy: tmp-smx, minocycline, newer quinolone
799
Organism
Preferred therapy
Staphylococcus#
(continued)
Vancomycin- Notify Infection
intermediate Control immedior resistant
ately; obtain
staphyloinfectious disease
cocci
consultation
StenotrophoMay be a colonizer;
monas
tmp-smx (consider
maltophilia
adding ticarcillinclavulanate for
severe infection)
Streptococcus
pneumoniae
PenicillinPenicillin, ampisusceptible
cillin
(MIC <0.1)
Alternative agents
(depending on
susceptibility)
Ticarcillin-clavulanate,
tigecycline, quinolone,
minocycline
Cephalosporin, a macrolide, tmp-smx, clindamycin, doxycycline,

newer quinolone, or any
of agents below in either
column
PenicillinCeftriaxone, cefoCefepime, vancomycin,
intermediate taxime, newer
linezolid, dalfopristinquinupristin, telithro(MIC
quinolone,
0.1- 2)
high-dose penicillin mycin, carbapenem*
or ampicillin,
amoxicilln (nonVariable resistance with
meningeal infecmacrolides, tmp-smx,
tion)
or clindamycin
PenicillinMeningitis: vanco- Linezolid, dalfopristinhigh-level
mycin + ceftriaxone, quinupristin
resistance
cefotaxime
(MIC >2)
rifampin
Other infections:
newer quinolone,
vancomycin
cefotaxime/
ceftriaxone
800
IV THERAPY
Organism
Preferred therapy
Streptococcus
Penicillin
group A, B, C,
or G
Alternative agents
(depending on
susceptibility)
Cephalosporin, other
penicillin class drug,
macrolides or clindamycin (variable resistance),
vancomycin, linezolid,
daptomycin
Cephalosporin, vancomycin, newer quinolone
Streptococcus
Penicillin
viridans group For endocarditis,
base treatment on
susceptibility testing
(see Circulation.
2005;111:e394e434)
Treponema
Penicillin
Doxycycline, ceftriaxone
pallidum
(syphilis)
Ureaplasma
Macrolide,
doxycycline
Vibrio cholerae Doxycyclne
Quinolone, tmp-smx
Vibrio vulnificus Doxycycline
Ceftriaxone, cefotaxime,
ciprofloxacin
Yersinia
Quinolone, gentaChloramphenicol, ceftrienterocolitica
micin, tmp-smx,
axone, cefotaxime
doxycycline
Yersinia pestis
Streptomycin
Tmp-smx, gentamicin,
(plague)
doxycycline, chloramphenicol, ciprofloxacin
CNS, central nervous system; ESBL, extended spectrum -lactamase; MIC,

mean inhibitory concentration; MRSA, methicillin-resistant Staphylococcus
aureus; MRSE, methicillin-resistant Staphylococcus epidermidis; tmp-smx,
trimethoprim-sulfamethoxazole.
*Carbapenems: meropenem, imipenem, ertapenem (ertapenem is not active
against Pseudomonas or Acinetobacter).
-Lactam-lactamase inhibitors: piperacillin-tazobactam (Zosyn), ampicillin-sulbactam (Unasyn), amoxicillin-clavulanate. Ticarcillin-clavulanate
(Timentin) is an agent and does not have good enterococcal coverage.
Macrolides: erythromycin, clarithromycin, azithromycin.
801
Footnotes (continued)
Gentamicin or streptomycin is added when cidal activity is required (e.g.,
endocarditis) and agents are susceptible for synergy.
//Daptomycin: insufficient data for serious enterococcal infections. Do not
use for pneumonia (high failure rates).
Newer (respiratory) quinolones: moxifloxacin, levofloxacin, gatifloxacin.
#Rifampin may be added for deep-seated staphylococcal infections (e.g.,
endocarditis) that are not responding well or in the presence of prosthetic
material. Coagulase-negative staphylococci are common contaminants but
can also cause serious infection.
Fungal Organism-Specific Treatment
Organism
Aspergillus
Blastomyces
Systemic
infection
Candida
unspeciated
C. albicans
C. tropicalis
or C.
parapsilosis
C. glabrata
C. krusei
C. lusitaniae
or C. guilliermondii
802
Preferred therapy
Alternative agents
(depending on
susceptibility)
Voriconazole
Amphotericin product,* itraconazole,

caspofungin,
posaconazole
(investigational)
Amphotericin product* Voriconazole, flu(life-threatening or
conazole
CNS disease)
Itraconazole (for mildmoderate disease)
Fluconazole (stable
patient), caspofungin
(in life-threatening/
unstable patient)
Fluconazole, caspofungin (in lifethreatening/unstable
patient)
Caspofungin, voriconazole, higher dose
fluconazole
Caspofungin, voriconazole
Voriconazole, fluconazole
Voriconazole, amphotericin product,* itraconazole, micafungin

Amphotericin product,* voriconazole,
itraconazole, micafungin
Amphotericin product,*, // itraconazole,
micafungin
Amphotericin product,*, // micafungin
Caspofungin, amphotericin product,*, //
micafungin
IV THERAPY
Organism
Systemic
infection
(continued)
Oropharyngeal/
thrush
Preferred therapy
Topical nystatin, clotrimazole, fluconazole
Esophagitis
Fluconazole
Urinary
tract
infection
Vulvovaginal
infection
Coccidioides
Fluconazole
Cryptococcus
Fusarium
Histoplasma
Intravaginal azole,
fluconazole
Fluconazole, itraconazole, amphotericin
product* (initial
therapy for diffuse/
disseminated diseases)
Fluconazole, amphotericin product*
(often with flucytosine for induction
therapy for CNS
disease)
Voriconazole, amphotericin product*
Itraconazole, amphotericin product*
Alternative agents
(depending on
susceptibility)
Voriconazole, amphotericin (PO liquid),

itraconazole, caspofungin, micafungin
Voriconazole, amphotericin product,*
itraconazole, caspofungin, micafungin
Amphotericin product*
Itraconazole, intravaginal boric acid

(refractory cases)
Voriconazole
Itraconazole, voriconazole
Fluconazole (after
amphotericin
induction for
CNS disease),
voriconazole
803
Organism
Preferred therapy
Paracoccidioides Itraconazole
Scedosporium
(Pseudallescheria)
Sporothrix
Zygomycetes
(Mucor)
Voriconazole
Itraconazole, amphotericin product*

Amphotericin
product*, //
Alternative agents
(depending on
susceptibility)
Voriconazole, sulfonamide, amphotericin
product* (with maintenance sulfonamide
or azole), ketoconazole, terbinafine
Itraconazole, terbinafine (in combo with
azole)
Posaconazole
(investigational)
CNS, central nervous system; MIC, mean inhibitory concentration.

*Amphotericin products include amphotericin B deoxycholate, liposomal
amphotericin (Ambisome), and amphotericin B lipid complex (Abelcet is
nonformulary).
Speciation and susceptibility testing for serious infections is recommended.
Caspofungin may display higher MICs for C. parapsilosis and C. guilliermondii; clinical implication is unclear.
Fluconazole and itraconazole MICs for C. glabrata are often in the susceptible but dose-dependent category. If used, higher than usual doses are suggested. If susceptibility results show susceptible isolate (MIC 8 for fluconazole or <0.125 for itraconazole), usual doses can be used.
//May exhibit higher MICs to amphotericin; consider use of higher-than-usual
doses.
Do not use topical therapy (e.g., nystatin, clotrimazole, amphotericin PO
suspension) for esophageal disease. Systemic therapy is needed.
804
IV THERAPY
Viral Organism-Specific Treatment (non-HIV Infections)
Organism
Preferred therapy
Cytomegalovirus Ganciclovir, valgan(CMV)

ciclovir
Alternative agents
Foscarnet, cidofovir,
ganciclovir implant*
(Vitrasert), fomivirsen*
(Vitravene implant)
Foscarnet (acyclovirresistant strains),
trifluridine eye drops
(for keratoconjunctivitis), ganciclovir,
valganciclovir
Entecavir, lamivudine,//
adefovir, tenofovir,
emtricitabine,# interferon
alpha
Herpes simplex
virus (HSV)
Acyclovir, famciclovir, valacyclovir
Hepatitis B
virus
Pegylated interferon
Hepatitis C
virus
Influenza virus
(treatment or
prophylaxis)
Pegylated interferon
+ ribavirin
Rimantadine (infl A), Zanamavir (infl A or B)
amantadine (infl A),
oseltamivir (infl A
or B)
Acyclovir, famcic- Foscarnet (acyclovirlovir, valacyclovir
resistant strains)
Varicella-zoster
virus (VZV)
Infl, influenza.
*Ocular inserts for CMV retinitis should generally be used in combination
with systemic therapy to prevent spread to contralateral eye and other
organs.
IV acyclovir should be used for HSV central nervous system disease and for
sight-threatening or severe VZV disease in immunocompromised patients.
Active against acyclovir-susceptible strains for HSV but not preferred agents
because of toxicity and cost.
Hepatitis B vaccine should be administered as preventive strategy to those at
risk (including health care workers).
//Lamivudine is approved by U.S. Food and Drug Administration for hepatitis
B and is also a good option to include in an HIV treatment regimen for
patients infected with hepatitis B.
Not approved for hepatitis B but may be reasonable option to include an
antiretroviral regimen in HIV-infected patients.
805
806
Appendix 3. Novel Bacterial Drug Resistance Mechanisms

Selected Bacterial Resistance Issues*
Pertinent organisms
E. coli, Klebsiella, Serratia
Resistance issue*
Treatment
Extended spectrum -lactamaseproducing (ESBL) gram-negative bacilli

Generally resistant to penicillins and cephalosporins Preferred: a carbapenem (meropenem,
May appear susceptible to piperacillin-tazobactam,
imipenem), but some regions have seen
but data from case series and observational
carbapenem resistance in Klebsiella
reports indicate a potentially higher failure rate
Alternatives: a fluoroquinolone, but there is
than with carbapenem therapy
less clinical experience
Enterobacter & Citrobacter

(less commonly, Morganella
spp, Providencia spp,
Serratia)
Inducible AmpC-mediated resistance in gram-negative bacilli

3rd-generation cephalosporins (e.g., ceftazidime,
Preferred: a carbapenem (meropenem,
cefotaxime, ceftriaxone) should generally be
imipenem, or ertapenem)
Alternatives: depending on susceptibility
avoided even if they are reported as susceptible
There is potential for induction or selection of
testing: quinolones, tmp-smx, piperacillinampC-mediated -lactamase (de-repressed
tazobactam, aminoglycosides, cefepime (better
-lactamase production) which can lead to
activity than 3rd-generation cephalosporins)
development of resistance while on therapy
If inducible resistance occurs, carbapenems are
typically the only active -lactams
Pertinent organisms
S. aureus
Enterococcus
Treatment
Methicillin-resistant Staphylococcus aureus

Oxacillin (methicillin)-resistant staphylococci are
Preferred: vancomycin, linezolid
resistant to all -lactam antibiotics
Alternatives (depending on susceptiBoth nosocomial & community-acquired strains are seen bility): minocycline, tmp-smx,
Community-acquired MRSA isolates tend to be more
clindamycin (need to test for inducible
susceptible to non-lactams (e.g., tmp-smx, clindamyresistance), daptomycin, & dalfocin, quinolones) than nosocomial isolates
pristin-quinupristin, tigecycline, newer
quinolone//
Vancomycin intermediate or vancomycin-resistant staphylococci
Contact Infection Control immediately
Organisms with reduced susceptibility or complete
and obtain an infectious disease
resistance to vancomycin have been reported
consultation
Reportable to State Dept. of Health
807
Vancomycin-resistant enterococci
Enterococci with resistance to vancomycin
Can cause invasive infection but can also be a colonizer
Colonizers (e.g., positive stool cultures) do not require
treatment
Preferred: linezolid
Alternatives: daptomycin, dalfopristinquinupristin (for E. faecium only),
tigecycline; can use penicillin/ampicillin
if susceptible
IV THERAPY
S. aureus with
vancomycin
MIC >4
Resistance issue*
808
Pertinent organisms
Stenotrophomonas
maltophilia
Resistance issue*
Stenotrophomonas
Can cause invasive disease but is a frequent colonizer
Colonizers do not typically require treatment
If treatment required, this organism is typically multidrug resistant and treatment should be guided by
susceptibility testing
Treatment
Preferred: tmp-smx, ticarcillin-clavulanate,
tigecycline
Alternatives (depending on susceptibility):
quinolones, minocycline
MIC, mean inhibitory concentration; tmp-smx, trimethoprim-sulfamethoxazole.

*See also institutional policies and procedures on microorganisms requiring isolation or contact an Infection Control officer.
May show in vivo susceptibility to cephamycins (cefotetan, cefoxitin), but failures have been reported and other mechanisms can confer resistance.
Cefepime is less likely to induce resistance than 3rd-generation agents, but resistance has been reported. If inducible -lactamase production occurs,
organisms should be considered resistant to penicillins and -lactams.
Daptomycin should not be used for pneumonia because of lack of penetration and higher failure rates. It has in vitro activity against enterococci, but
studies are very lmited for serious enterococcal infections.
//Newer quinolones: moxifloxacin, levofloxacin, gatifloxacin, gemifloxacin. Staphylococcal resistance to quinolones has been reported to develop while
patient is receiving therapy.
IV THERAPY
CARDIAC ARREST
Patient survival is critically dependent on first responders

and actions taken in the first few minutes after cardiac arrest.
Most adult patients with sudden cardiac arrest have unstable
ventricular tachycardia (VT) or ventricular fibrillation (VF),
more rarely asystole or pulseless electrical activity (PEA)
(formerly called electromechanical dissociation).
Immediate cardiopulmonary resuscitation (CPR) is the best
treatment for cardiac arrest until defibrillation and advanced
cardiac life support (ACLS) can be instituted.
Early effective CPR improves patient survival in cardiac
arrest by delaying rhythm degeneration from VF into asystole, preventing acidosis, and reducing anoxic brain damage.
Early defibrillation is the most important determinant of
survival after cardiac arrest
Survival following VF decreases by about 8% for each
minute without defibrillation.
Survival after VF for >15 minutes is <5%
Cardiac arrest victims with hypothermia, usually associated
with drowning or cold weather exposure, are partially
protected and may be successfully resuscitated after longer
periods of time.
BASIC LIFE SUPPORT FOR ADULTS

Check responsiveness.
Activate emergency response system.
Check airway.
Special abbreviations used in this chapter: ACLS, advanced cardiac life support;
CPR, cardiopulmonary resuscitation; PEA, pulseless electrical activity; VF,
ventricular fibrillation; VT, ventricular tachycardia.
809
Check breathing.
Give two effective breaths.
Check circulation.
Compress chest if no signs of circulation are detected.
An unresponsive patient who is breathing and has adequate
circulation should be placed in the lateral position to prevent airway obstruction.
A patient with absent respiration requires rescue breathing
provided at 10-12 inhalations per minute. Significantly faster
rates of rescue breathing are less beneficial.
Assess circulation by palpation of the carotid artery. If in
doubt about the status of the carotid pulse in an unconscious
patient, start chest compressions.
CHEST COMPRESSIONS
Rhythmic pressure over the lower half of the sternum
Compression rate of 100/minute
Ratio of 15 compressions to 2 ventilations
Compress sternum approximately 2 inches and assess adequacy of compression by palpating carotid or femoral pulse.
Effective chest compression produces a systolic blood
pressure of about 70 mm Hg and a cardiac output about onethird of normal.
Do not interrupt CPR for more than 10 seconds except to
defibrillate.
After each compression, chest pressure must be completely
released.
The most effective cerebral and coronary perfusion is
achieved when 50% chest compression phase and 50% chest
relaxation phase.
COMPLICATIONS OF CPR
Inadequate chest compression
Gastric inflation resulting from excessive ventilation
Regurgitation of gastric contents and lung aspiration
Rib fractures, sternum fracture, separation of ribs from
sternum
Pneumothorax, hemothorax
Lung contusions, laceration of liver and spleen
Defibrillation burns
Dental injury from traumatic intubation
810
IV THERAPY
ACLS
DEFIBRILLATOR
Defibrillate up to three times for VF/VT, using energies of 200
J, 300 J, and 360 J for monophasic defibrillators or a nonescalating energy of 150-170 J for biphasic defibrillators (preferred option).
After three shocks, CPR should be resumed for at least 1
minute; after this period, the rhythm should be reassessed
and repeat shock delivered if appropriate.
Defibrillation should be attempted after each medication is
administered or after each minute of CPR.
DRUG THERAPY OF CARDIAC ARREST
Drug therapy is second-line therapy for cardiac arrest.
Epinephrine can be administered at 1 mg IV every 3-5
minutes for PEA, asystole, or refractory VF/VT not responding to defibrillation.
DEFIBRILLATION-REFRACTORY VT/VF
Amiodarone300 mg IV push. If VF or pulseless VT recurs,
a second 150-mg dose can be administered.
Lidocaine1 mg/kg IV push. This dose can be repeated
every 3-5 minutes up to a maximum dose of 3 mg/kg.
Magnesium sulfate1-2 g IV is recommended for treatment
of polymorphic VT (torsades de pointes) and suspected low
magnesium.
Sodium bicarbonate1 mEq/kg IV is indicated for hyperkalemia, metabolic acidosis, or aspirin or tricyclic antidepressant drug overdose.
Not routinely used for acute lactic acidosis associated with
CPR, but may be given to correct acidosis with shock-refractory VF/VT
PEA (ELECTROMECHANICAL DISSOCIATION)

Cardiac rhythm other than VT or VF in absence of a
detectable pulse
811
Consider
Pulmonary embolism
Cardiac tamponade
Hypovolemic shock
Septic shock
Hypokalemia and hyperkalemia
Hypothermia
Acidosis or hypoxia
Drug overdoses
Cardiac Medication Used in PEA
Epinephrine1-mg IV push every 3-5 minutes may be tried
for PEA.
Atropine1 mg every 3-5 minutes for PEA
ASYSTOLE
Asystole as the primary cause of cardiac arrest or following
VF/VT has a very poor prognosis.
PATIENTS FACTORS USED IN THE DECISION-MAKING

PROCESS FOR TERMINATION OF CPR
Duration of CPR >30 minutes
Initial ECG rhythm was asystole or asystole has now replaced
earlier VF/VT
Prolonged interval (>10-15 minutes) between estimated time
of arrest and initiation of CPR
Severity of comorbid disease
Absence of brainstem reflexes
Absence of hypothermia
Availability of living will or patients relatives to indicate
patients wishes in the event of cardiac arrest
812
IV THERAPY
INSULIN THERAPY FOR
HOSPITALIZED PATIENTS
Cacia V. Soares-Welch, M.D.
William C. Mundell, M.D.
CLASSIFICATION
SQ insulin is classified into rapid-, intermediate-, and longacting agents (Table 1).
IV insulinrapid-acting (the only insulin used IV)
Insulin pumpuses rapid-acting insulin
INDICATIONS FOR INSULIN
Hyperglycemia
Diabetic patient on usual diet
Diabetic patient who is NPO
Steroid-induced hyperglycemia
Parenteral nutrition-induced hyperglycemia
Nonketotic hyperosmolar syndrome
Acute hyperkalemia
MONITORING INSULIN THERAPY

Monitoring insulin therapy in various medical conditions is
described in Table 2.
If fingerstick glucose is <60 mg/dL or >400 mg/dL, check a
confirmatory serum glucose to determine exact glucose value.
PRESCRIBING INSULIN
The time and type of insulin prescribed are listed in Table 3.
A patient whose blood glucose level is well controlled at
home may become hypoglycemic when given the usual
insulin dose in the hospital on an American Diabetes
Association diet, which may be more restrictive than the
home diabetic diet.
Make sure that the meal is not delayed or missed when
patients receive insulin.
813
Table 1. Onset, Peak Action, and Duration of SQ Insulin

SQ insulin
Peak action,
hours*
Duration,
hours
0.25
0.25
0.5-1
0.5-1
1-3
1-3
2-6
3-10
3-6
3-6
4-12
8-16
2-4
3-4
6-16
6-16
14-28
14-28
3-8
4-20
10-40
3-8
3-8
14-26
4-24
24-40
11 to >24
Onset, hours
Rapid-acting
Lispro
Aspart
Regular
Semilente
Intermediate-acting
NPH
Lente
Long-acting
Ultralente (human
or bovine)
Protamine zinc
Glargine
*Peak effect varies from person to person and depends on dose.
Hyperglycemia
Goalrestore normal glucose
Stable diabetic patient on usual diet
Continue usual insulin therapy and use insulin supplementation as needed.
Critically ill diabetic patient
Continue usual insulin therapy and use insulin supplementation to achieve appropriate glucose control.
Do not withhold insulin, otherwise patient will be driven
into diabetic ketoacidosis!
Diabetic patient NPO for procedure
Withhold oral antihyperglycemic agent before the
procedure.
Give one-half the usual dose of intermediate-acting insulin
(NPH or Lente).
If fasting glucose is <100 mg/dL, add glucose to IV fluid
(5% dextrose in 0.45% normal saline at 100 mL/hour = 5
g of glucose/hour).
If fasting glucose is >200 mg/dL, give only supplemental
insulin (do not add to usual rapid-acting insulin dose).
After the procedure, resume the oral agent when patient is
able to eat.
814
Table 2. Monitoring Insulin Therapy in Various Medical Conditions

Medical condition
Stable
Critically ill
Perioperative period
Parenteral nutrition
1-2 times/day
4-5 times/day
In recovery room (preand postoperative)
2-4 times/day
2-4 times/day
Every 30-60 minutes
Every 30-60 minutes
30-60 minutes after
insulin administration
Also monitor
End point
RMG = 100-150 mg/dL
RMG = 100-120 mg/dL
RMG = 100-180 mg/dL
Electrolytes daily
Electrolytes every 1 hour;
Urine output
Electrolytes every 1 hour
Potassium every 1 hour
NKHS, nonketotic hyperosmolar syndrome; RMG, reflectance meter glucose.
RMG = 100-150 mg/dL

RMG = 100-150 mg/dL
Resolution of acidosis
RMG = 100-150 mg/dL
Stabilization of hyperkalemia
815
IV THERAPY
NKHS
Acute hyperkalemia
Frequency of RMG
Table 3. Time and Type of Insulin Prescribed

Time and type of insulin
Glucose value affected
Rapid acting
NPH or Lente
PM Rapid acting
PM NPH or Lente
Lunch glucose
Supper glucose
Bedtime glucose
Breakfast glucose
AM
AM
Perioperative period (coordinate with the anesthesiologist)

Goal blood glucose = 120-200 mg/dL
Measure preoperative and postoperative (recovery room)
blood glucose level.
Patients usually on diet or oral agent control (type 2)
Withhold oral antihyperglycemic agent before the
procedure.
If preoperative glucose is >200 mg/dL, add 5-10 U regular insulin per 50 g glucose (1 L of 5% dextrose) in IV or
give 5-10 U of short-acting insulin SQ.
If postoperative glucose is >200 mg/dL, continue adding
5-10 U regular insulin per 50 g glucose in IV and give
short-acting insulin SQ every 4-6 hours.
Patients usually on insulin control
If preoperative glucose is >200 mg/dL, add 5-10 U regular insulin per 50 g glucose in IV (e.g., 5% dextrose in
0.45% normal saline with 20 mEq KCl/L at 100 mL/hour
= 5 g glucose/hour).
Give 1/2 the total AM intermediate insulin dose preoperatively.
Use rapid-acting insulin supplement for the first day postoperatively.
Goalfasting blood glucose <150 mg/dL
Use supplemental regular insulin for the first day.
On the second day, add the amount of insulin used the
first day and divide the total amount into 2/3 in the morning and 1/3 at supper.
Continue to adjust the dosages daily based on amount of
supplemental insulin needed and steroid doses.
Parenteral nutrition-induced hyperglycemia
816
IV THERAPY
Add 0.1 U regular insulin per 1 g glucose in total parenteral nutrition (e.g., 20 U/L; dextrose 20% is 200 g/L).
Add SQ insulin if reflectance meter glucose is >150 mg/dL
on full total parenteral nutrition insulin coverage.
An algorithm for calculating the amount of supplemental
insulin is given in Figure 1.
Another way to calculate the amount of supplemental insulin
is the 1,500 rule:
Divide 1,500 by the total daily insulin usually required
by the patient.
This is the amount the blood glucose will decrease when
1 U of rapid-acting insulin is given SQ.
For example, total daily insulin = 50 U
1,500/50 = 30
1 U of rapid-acting insulin will decrease blood glucose
by 30 mg/dL.
Goalresolve acidosis
Initial dose10-15 U (or 0.15 U/kg) rapid-acting insulin IV
bolus
Continuous dose10 U/hour (or 0.1 U/kg per hour) IV or IM
rapid-acting insulin
Rate of glucose decrease should not exceed 80-100 mg/dL
per hour.
If glucose decreases >100 mg/dL per hour, continue insulin
infusion and add 5% dextrose to IV fluids.
As glucose approaches 250-300 mg/dL, add 5% dextrose
to IV fluids.
Maintain blood glucose at 200-300 mg/dL.
Increase insulin dose by 50%-100% per hour if insulin resistance is suspected.
When serum bicarbonate >15 mEq/L, change insulin to 1-2
U/hour.
Maintenance dose for diabetic patients
Start usual insulin regimen when acidosis has resolved
(ketones are no longer present in serum), and discontinue insulin drip 1 hour after SQ insulin is given.
817
818
Measure fingerstick blood glucose

(RMG) 15-30 min before meal
<200 mg/dL
No supplemental insulin
needed
200-300 mg/dL
>300 mg/dL
Add 0.075 U/kg rapidacting insulin to usual

insulin dosage
Add 0.1 U/kg rapidacting insulin to usual

insulin dosage
Measure RMG 2 hours after meal

to evaluate effectiveness of
insulin dose
Fig. 1. Algorithm for calculating supplemental insulin. RMG, reflectance meter glucose.
IV THERAPY
Maintenance dose for newly diagnosed diabetic patients

First 24 hours0.1-0.25 U/kg rapid-acting insulin every
6-8 hours to determine a daily insulin requirement
Second 24 hours
1/2 the previous days total dose in the morning (1/3
rapid-acting, 2/3 intermediate-acting) and
1/2 the previous days total dose in the evening (1/2
rapid-acting, 1/2 intermediate-acting)
or
The previous days total dose divided as 1/4 rapidacting at breakfast, 1/4 rapid-acting at lunch, 1/4 rapidacting in the evening, and 1/4 intermediate-acting at
bedtime
Nonketotic Hyperosmolar Syndrome

Goalrestore normal glucose
Initial dose5-10 U IV regular insulin bolus if glucose is
>600 mg/dL
Continuous dose5-10 U/hour IV or IM to lower glucose to
~200 mg/dL
Maintenance doseSQ insulin
Fluid repletion is the most important aspect of treatment.
COMPLICATIONS OF INSULIN THERAPY

Hypoglycemia
Symptoms and signsdiaphoresis, tremors, tachycardia,
confusion, seizure, stupor, coma, etc.
Diagnosis
Stat measurement of plasma glucose
Plasma glucose <70 mg/dL
Treatment
15 g of fast-acting oral carbohydrate (1 cup of milk or
juice, cheese and crackers) if patient is alert
or
IV dextrose (25-50 mL 50% dextrose) if patient is NPO or
unable to swallow. Then infusion of 5% dextrose in water
or
Glucagon 1 mg IM or SQ
819
Monitoring
Retest reflectance meter glucose 15 minutes after treatment.
If <70 mg/dL, repeat above treatment.
If >70 mg/dL and >30 minutes to meal or snack, give 15
g of carbohydrate + protein.
If >70 mg/dL and <30 minutes to meal or snack, proceed
with meal or snack.
Allergic Reaction
Symptoms and signs
Localerythema, induration, and pruritus at injection site
Systemicurticaria, angioneurotic edema, and anaphylaxis
Diagnosisclinical exam
Treatment
Localantihistamine
Switch to biosynthetic human insulin if animal insulin
was used originally.
Desensitization may be needed.
Systemicsupportive care, antihistamine, epinephrine
and/or corticosteroids if needed
Insulin desensitization is mandatory.
Hypokalemia
Make sure the serum potassium level is normal before insulin
administration and measure the serum potassium level
frequently.
Correct potassium as needed.
820
IV THERAPY
LIPID MANAGEMENT
Atherosclerosisdiffuse inflammatory-proliferative arterial reaction initiated by endothelial injury

Atherosclerotic lesions that appear focal and limited on coronary angiography are pathologic, widespread within the arterial tree.
Risk factor modification, especially low-density lipoprotein
(LDL), high-density lipoprotein (HDL), and triglyceride
optimization, is mandatory for all patients with atherosclerosis irrespective of presentation syndrome.
CLASSIFICATION OF DYSLIPIDEMIA
Dyslipidemiaa heterogeneous disorder with multiple
causes.
In Western societies, most dyslipidemia is secondary to
lifestyle and poor dietary habits.
Physiologic LDL is probably in the range of 50-70 mg/mL,
as determined by findings in non-westernized societies where
atherosclerosis is unknown.
Most patients have mixed dyslipidemia: frequently elevated
LDL cholesterol in combination with low HDL cholesterol
and/or elevated serum triglyceride.
Many patients with dyslipidemia have multiple confounding
medical issues such as diabetes or metabolic syndrome,
obesity, hypertension, and occasionally, obstructive sleep
apnea, all of which necessitate treatment.
Dietary reductions in saturated fat and total caloric content
typically reduce LDL cholesterol values 10%-15% and
plasma triglycerides can fall 20%-40%.
Special abbreviations used in this chapter: HDL, high-density lipoprotein; LDL,

low-density lipoprotein.
821
Regular, vigorous exercise can raise HDL cholesterol values

by 10%-15%, comparable to changes induced by pharmacologic therapy.
Diet therapy, undoubtedly effective in a highly motivated
person, fails to achieve goal LDL levels in most patients.
PHARMACOLOGIC TREATMENT OF DYSLIPIDEMIA

Goal-directed therapy for dyslipidemia is outlined in Table 1.
Statins
Statin agents work through at least two mechanisms in
patients with dyslipidemia.
Statins inhibit the enzyme responsible for the rate limiting step of cholesterol biosynthesis and HMG coenzyme
A reductase and thus directly inhibit cholesterol biosynthesis.
Statins promote LDL receptor upregulation on hepatocytes
and thus promote biologic clearance of LDL-cholesterol.
Statins typically lower LDL-cholesterol 25%-55%
Statins lower total cholesterol similarly in magnitude to that
observed with LDL-cholesterol.
Statins also increase HDL-cholesterol by 5%-15%.
Potent statins may reduce plasma triglycerides 15%-45%.
Statins are associated with elevation of liver enzymes and
rarely rhabdomyolysis.
Niacin
Niacincurrently the most potent U.S. Food and Drug
Administrationapproved HDL-cholesterol raising drug
available.
Treatment with niacin increases HDL-cholesterol 20%-30%
in most patients and decreases plasma triglycerides 30%40%.
Niacin also reduces plasma LDL-cholesterol an additional
20%-30%.
Niacin is generally well tolerated if started at lower doses
and gradually increased over time.
Aspirin pretreatment reduces flushing and headache
frequently seen with niacin.
Niacin can be used safely in combination with statins, fibrates,
and ezetimibe.
822
IV THERAPY
Table 1. Goal-Directed Therapy for Dyslipidemia*
Goals
Patients
LDL,
mg/dL
HDL,
mg/dL
With established
CAD
70
40
With diabetes
mellitus or
hypertension but
not CAD events
70-100
40
With diabetes
mellitus or
hypertension +
known CAD
70
40
Populations with
multiple cardiovascular risk
factors or family
history of severe,
premature CAD
100
40
Therapy
Statin
or
Statin + ezetimibe
Statin
or
Statin + ezetimibe
or
Statin + fibrate
Statin
or
Statin + ezetimibe
or
Statin + fibrate
Statin
or
Statin + niacin
or fibrate
CAD, coronary artery disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
*All patients should be educated about and adhere to AHA Step 2 Diet.
All patients should reduce body weight to body mass index 25.
All patients should exercise 4-5 times per week for at least 30 minutes per
session.
All patients should stop using any tobacco products.
Fibrates
Fibrates
Gemfibrozil and fenofibrate are potent triglyceridelowering agents.
They reduce plasma triglycerides 40%-60% when utilized
with dietary modification.
Fibrates also increase HDL-cholesterol by additional 10%20% but are generally less effective than niacin for this
situation.
823
Rare but serious cases of rhabdomyolysis have been

reported with combination statins and fibrates.
Ezetimibe
Directly inhibits cholesterol absorption in small intestine
and lowers plasma LDL-cholesterol additional 15%-20%
when used with a statin
Resin-Binding Agents
Cholestyramine and colestipol decrease total cholesterol and
LDL-cholesterol by binding bile acids in intestine to interrupt
enterohepatic circulation of bile acids. This action stimulates
a secondary increase in hepatic LDL receptors, which in
turn remove LDL-cholesterol from the circulation.
Resins have no important effect on HDL but increase plasma
triglycerides.
Major side effects of resins: gastrointestinal intolerance with
gas, bloating, constipation, nausea, and esophageal reflux
Resins inhibit absorption of vitamin K, digoxin, warfarin,
thyroxine, and diuretics
824
IV THERAPY
MECHANICAL AND NONINVASIVE
POSITIVE PRESSURE VENTILATION
Steve G. Peters, M.D.
MECHANICAL VENTILATION
The initiation of intubation and mechanical ventilation is an
attempt to accomplish one, or all, of the following:
Protect the airway or overcome airway obstruction
Support or maintain pulmonary gas exchange
Increase lung volume
Reduce the work of breathing
Indications
Acute respiratory failure
Respiratory activity is insufficient to maintain adequate
oxygenation or ventilation (carbon dioxide clearance)
Develops over a short period
Hypercapneic (hypercarbic) respiratory failurea reflection of inadequate ventilation, e.g., alveolar hypoventilation
When acute, a rapid rise in PaCO2, with an accompanying drop in arterial pH (assuming no metabolic component), is observed.
Clinical signs include recruitment of accessory respiratory muscles, mental status changes, agitation, tachypnea and, eventually, unresponsiveness.
Causes include three general groups of disorders:
Central nervous system disorders
Neuromuscular disorders
Disorders resulting in increased work of breathing
or characterized by increased alveolar dead space (in
Special abbreviations used in this chapter: FIO2, fraction of inspired oxygen;

I:E, inspiratory-to-expiratory timing; NPPV, noninvasive positive pressure ventilation; PEEP, positive end-expiratory pressure; SIMV, synchronized intermittent mandatory ventilation.
825
which total minute ventilation might seem adequate

but alveolar ventilation is reduced)
Hypoxemic respiratory failurethe inability to maintain
adequate arterial oxygenation
This can occur despite adequate ventilation as reflected
by a normal or low PCO2.
Clinical signs include tachypnea, dyspnea, cyanosis,
mental status changes, hypertension, and peripheral
vasoconstriction.
General anesthesia
Intentional hyperventilation (increased intracranial pressure,
although adaptive mechanisms render this treatment modality ineffective after 24-36 hours)
Common causes of hypercapneic and hypoxemic respiratory failure are listed in Table 1.
Ventilator Settings
The following parameters are typically set by the physician
on initiation of mechanical ventilation:
Tidal volume
This parameter is set directly by the physician or is
determined by the ventilator after the minute volume and
respiratory rate are set.
Table 1. Common Causes of Acute Respiratory Failure

Hypercapneic
Hypoxemic
Cerebrovascular accident
Head trauma
Drug effect
General anesthetics,
barbiturates
Paralytic agents
Aminoglycoside antibiotics
Corticosteroids
Chest wall deformity
Amyotrophic lateral sclerosis
Pulmonary fibrosis
Morbid obesity
Poliomyelitis
Ventilation-perfusion mismatch
ARDS
Pneumonia
Acute lung injury
Pulmonary edema
Diffusion defects
Right-to-left shunts
Aging
Hypoventilation
Inadequate FIO2
ARDS, acute respiratory distress syndrome; FIO2, fraction of inspired oxygen.

826
IV THERAPY
Tidal volume cannot be set in pressure control ventilation; it is determined by the amount of pressure given,
the lung and chest wall compliance, and the inspiratory effort.
Generally, 10-12 mL/kg ideal body weight is used for
mechanically ventilated patients.
Low tidal volumes set at 6 mL/kg ideal body weight
improve survival in acute lung injury and acute respiratory distress syndrome.
Fraction of inspired oxygen (FIO2)
Generally, this should be set for 100% for most patients
initiated on mechanical ventilation.
Further adjustments are guided by arterial blood gas
measurements and pulse oximetry.
To avoid oxygen toxicity, it is prudent to reduce FIO2
to 0.6.
Respiratory rate
This is set once the physician has considered inspiratoryto-expiratory ratio (I:E) and the patients own respiratory rate.
Ventilator backup rate should be close to the patients
actual respiratory rate.
Inspiratory flow rate
After patient-ventilator interactions have been observed,
this is generally set to minimize patient-ventilator
asynchrony.
In pressure-cycled modes, this is not a set variable.
Inflation pressure setting
Inflation pressure is a dependent function of volume
with volume-cycled ventilation and is preset with pressure-preset modes.
Generally, keep inflation pressures <35 cm H2O to
decrease risk of barotrauma.
Coughing and sneezing can cause random increases in
inflation pressure.
Positive end-expiratory pressure (PEEP)
This refers to application of a positive pressure at the end
of passive expiration.
827
When PEEP is not selected, airway pressure returns to

ambient atmospheric pressure.
PEEP is used to recruit atelectatic and flooded alveoli
to participate in gas exchange and improve oxygenation.
It can be used in any ventilator mode.
Intrinsic PEEP (auto-PEEP, breath stacking, dynamic hyperinflation)
Phenomenon of increased airway pressure at end of
exhalation without intentional selection of PEEP on
the ventilator
Detect intrinsic PEEP by occluding the exhaust port
of the ventilator at end-expiration just before the next
inspiration, observing the airway pressure.
Many ventilators have a feature that allows the ventilator to evaluate intrinsic PEEP with the push of a
button.
The main adverse effects of PEEP are decreased cardiac output (by decreasing preload), hypotension,
and barotrauma, including pneumothorax.
If intrinsic PEEP is present above the intentional
application of PEEP, these effects may be severe.
PEEP is usually titrated to the lowest level necessary to achieve adequate oxygenation (arterial saturations 90% or PO2 60 mm Hg with FIO2 <0.6).
Modes of Mechanical Ventilation
When discussing mechanical ventilation, some terms must
be defined to facilitate understanding of ventilator function.
Triggered
Refers to the initiation of the breath delivered by the
ventilator
Can be set by time, flow, motion (pediatric ventilators),
or pressure and can be initiated by the patient or the
ventilator
Ventilators can be triggered manually, usually by a push
button.
Cycled
Refers to the termination of the mechanical inspiratory breath and the beginning of exhalation
This is predetermined and is set, most commonly, as a
function of time (most ventilators measure how much
828
IV THERAPY
time it takes to deliver a preset volume at a preset flow

rate and, thus, are actually time-cycled).
Limited
Refers to a preset variable being reached before the end
of inspiration
A limit can be set as a function of flow, pressure, or volume.
Mechanical ventilation is a form of positive pressure ventilation, which is either volume-cycled or pressure-preset.
Volume-cycled ventilation
Provides a constant volume with each delivered breath
Airway pressure varies as a function of volume; thus, if
compliance of the lungs or chest wall decreases
(increased stiffness), airway pressure will increase
because a set volume is guaranteed.
Pressure-preset ventilation
Delivers a breath to a preset pressure that is limited
If a pressure-preset mode is used for the example above,
the volume will vary as a function of pressure. If compliance decreases, then volume will decrease because the
preset pressure is reached earlier during inspiration
(limited).
The usual modes of mechanical ventilation are listed below
with a brief description.
Assist/control ventilation
Preselected tidal volume, minimum respiratory rate and
inspiratory flow rate
Time- or patient-triggered
It is set to detect the patients inspiratory effort. Once
detected, this mode provides an assisted mechanical
breath until the preset tidal volume is delivered.
If no inspiratory effort is detected in a predetermined
amount of time (as determined by the minimum respiratory rate), the ventilator automatically delivers a
mechanical breath.
If the patients respiratory rate exceeds the preset minimum respiratory rate, all breaths will be assisted. If
apnea occurs, the patient receives the ventilators set
minimum respiratory rate.
829
830
Assist/control is indicated when it is desired that the

ventilator assume most or all the work of breathing,
e.g., neuromuscular weakness, paralysis, or respiratory muscle fatigue.
Some patients may develop respiratory alkalosis.
Alkalosis can be severe if the patient had preexisting
hypercapneic respiratory failure with compensatory
increase in bicarbonate.
Also, the assist/control mode poses the greatest risk
of air-trapping and dynamic hyperinflation for patients
with airflow obstruction.
Controlled mechanical ventilation
All parameters (tidal volume, inspiratory flow rate, I:E,
and respiratory rate), are determined entirely by the
operator and are machine set.
The only indication for this mode is to provide mechanical ventilation to a patient experiencing apnea.
Sedation and paralysis are usually required.
Synchronized intermittent mandatory ventilation (SIMV)
Preselected tidal volume or pressure and minimum respiratory rate
Time- or patient-triggered
Spontaneous breaths can be pressure-supported.
Sensitized to detect the patients inspiratory effort, but
unlike the assist/control mode, only assists the patients
effort at the minimum respiratory rate preset on the ventilator (e.g., if this rate is 8 and the patient is making 22
inspiratory efforts per minute, only 8 of these efforts will
be assisted. Any full breaths over the rate of 8 are breaths
that the patient achieves alone. If the patient becomes
apneic, the ventilator will deliver 8 breaths per minute)
The breaths are synchronized with the patients inspiratory efforts to avoid a double breath.
Allows for spontaneous breathing between ventilatorassisted breaths
Between ventilator-assisted breaths, the ventilator provides warm, humidified air with a predetermined FIO2.
SIMV was developed initially as a weaning mode;
the minimum respiratory rate could be gradually reduced.
The most useful functions of this mode may be when
a patient needs substantial respiratory support and
IV THERAPY
has a very high respiratory rate or when it is desirable

for the patient to assume some of the work of breathing to preserve respiratory muscle function.
Pressure control ventilation
Preselected pressure, minimum respiratory rate, and
duration of inspiration
Time- or patient-triggered, pressure-limited, and timecycled
Can be used with assist/control ventilation or SIMV
Ventilator raises airway pressure (detected at the endotracheal tube) to a level preselected by the physician.
If patient becomes apneic, the ventilator cycles at the
minimum respiratory rate and tidal volume will depend
entirely on the incremental increase in airway pressure in
addition to the compliance of the lungs and chest wall.
If the patient makes inspiratory efforts, tidal volume
will be a function of the intensity of the patients inspiratory effort as well as the incremental increase in airway
pressure and the compliance of the lungs and chest wall.
Patient has little control over tidal volume and pattern
of breathing (inspiratory time is preset), so generally
the patient must be sedated and paralyzed.
Useful when further lung injury by high pressures needs
to be avoided, as in acute lung injury and acute respiratory distress syndrome
In these situations, lung injury may be increased by
overdistension of lung tissues (barotrauma or volutrauma).
Pressure support ventilation
Preselected pressure to help achieve desired tidal volume with each spontaneously triggered breath thus
decreasing the work of breathing
The patient must be breathing spontaneously to use this
mode (always patient-triggered).
During exhalation, airway pressure returns to zero or the
preselected PEEP.
Patient has more control over inspiratory time, tidal
volume, and flow.
831
This may be a more comfortable mode of breathing for

patients.
It is frequently a weaning mode. The level of pressure
support is reduced gradually, allowing the patient to
assume more of the work of breathing.
Mechanical Ventilation Strategies
Commonly encountered clinical situations and typical ventilator strategies for which mechanical ventilation is used
Keep in mind that initial ventilator settings are suggested.
The clinical situation and arterial blood gas determinations should guide further ventilator adjustments.
Weaning
After the precipitating cause of acute respiratory failure has
resolved, fully 80%-90% of patients on mechanical ventilation can be weaned and extubated without difficulty.
Some patients can be extubated without a weaning process.
However, for a small group of mechanically ventilated
patients, the weaning process can be long and difficult.
Several weaning strategies have been used, the most common
being the following:
T-piece trials, in which periods of spontaneous breathing are alternated with partial, or full, ventilatory support
SIMV, in which the number of mandatory breaths is
decreased over hours to days
Pressure support ventilation, in which the amount of pressure support is decreased over hours to days and the patient
gradually assumes more of the work of breathing
Two studies have shown conflicting results with weaning
methods.
One studyPressure support ventilation is superior to
SIMV and T-piece trials.
Other studyT-piece trials are superior to the others.
Both studiesSIMV is inferior to other two methods.
Weaning trials should be attempted only when the patient is
hemodynamically stable, improving, awake and alert, cooperative, and informed that the weaning process is to take
place.
A recent study showed that daily interruption of sedative
832
Table 2. Mechanical Ventilation Strategies

Scenario
Modes
Initial settings
VT 10-12 mL/kg
f 20-25 breaths/minute (intentional
hyperventilation)
PEEP 0-5 cm H2O
FIO2 1.0 initially
Asthma
A/C, PCV
COPD
A/C, SIMV, PCV
VT 6-8 mL/kg
f 12-16 breaths/minute
Q 60-100 L/minute
FIO2 1.0 initially
PPLAT <35 cm H2O
VT 8-10 mL/kg
PPLAT <35 cm H2O
Q 60 L/minute
PAO2 60-70 mm Hg
PEEP 2.5-5 cm H2O
Goals/comments
Avoid high intrathoracic pressure which
impedes venous return from the brain
(ICP monitored and <10)
Increase FIO2 rather than PEEP for
hypoxemia
If ICP not elevated, intentional hyperventilation not indicated
Volume or pressure ventilation may be
used
Permissive hypercapnia? If used, keep
pH 7.1-7.2
If intrinsic PEEP observed, increase
expiratory time
Maintain CO2 at patients baseline
Prone to intrinsic PEEP
IV THERAPY
833
Head injury/trauma A/C, SIMV
834
Table 2 (continued)
Scenario
ARDS
CHF/pulmonary
edema
ARF
Modes
Initial settings
VT 5-8 mL/kg (volume-cycled)

PIP <40 cm H2O (pressure preset)
PEEP no upper limit
A/C, SIMV (? NPPV) VT 8-12 mL/kg
Q 60 L/minute
FIO2 1.0 initially
PEEP 5-10 cm H2O
A/C, SIMV, PCV
VT 8-10 mL/kg (volume-cycled)
PIP 10-15 cm H2O (pressure
preset)
PEEP 5-10 cm H2O
FIO2 1.0
PCV, A/C
Goals/comments
May need sedation and/or paralysis
Permissive hypercapnia? Proning?
If sedated/paralyzed, use lower respiratory rates
Keep O2 saturation 90% at FIO2 <0.6
PEEP applied to recruit flooded & collapsed lung
units
Volume or pressure ventilation may be used
Restore adequate ventilation & oxygenation

Monitor for intrinsic PEEP
A/C, assist/control; ARDS, acute respiratory distress syndrome; CHF, congestive heart failure; f, frequency; FIO2, fraction of inspired oxygen; ICP,
intracranial pressure; NPPV, noninvasive positive pressure ventilation; PCV, pressure control ventilation; PIP, peak inspiratory pressure; PPLAT, plateau
pressure; Q, flow rate; SIMV, synchronized intermittent mandatory ventilation; VT, tidal volume.
IV THERAPY
infusions shortened the time of mechanical ventilation

and length of stay in the ICU.
Physiologic parameters that help determine a patients
readiness for weaning are listed in Table 3.
The index of rapid shallow breathing (f/VT) is the most sensitive and specific single predictor of weaning success.
Factors to be considered in the weaning process are as
follows:
Prepare the patient.
The patient must be reassured that ventilatory backup
is immediately available in the event of a failure.
Communicate to the patient that the weaning process is
gradual and progressive.
Encourage and support the patient.
Address nonrespiratory factors that may contribute to
weaning failure, e.g., cardiac status, acid-base and metabolic status, drugs (sedatives, narcotics, etc.), nutrition,
and psychologic dependency.
Therapist-driven protocols have been found to shorten the
time of mechanical ventilatory support and to reduce hospital costs.
The patients pain level (recent thoracic or abdominal
surgery)
After a weaning trial is under way, signs of clinical deterioration, which may indicate the need for reinstitution of ventilatory support, include
Table 3. Weaning Parameters

Patient alert, cooperative, improving
FIO2 requirement 0.50
Maximum inspiratory pressure < 10 to 20 cm H2O
PEEP requirement <5 cm H2O
f/VT <100 (VT measured in liters)
Respiratory rate <25 breaths/minute
Minute ventilation <10-20 L/minute
FIO2, fraction of inspired oxygen; f/VT, respiratory rate/tidal volume (index
of rapid shallow breathing); PEEP, positive end-expiratory pressure.
835
Subjective dyspnea, rated 5/10 by the patient

Heart rate >30 beats/minute above baseline
Ventricular ectopy, supraventricular tachyarrhythmias
Arterial oxygen saturation <90%
Respiratory rate >35 breaths/minute for at least 5 minutes
Clinical judgment must be used when interpreting these
signs, which are not absolute.
It is important not to terminate a weaning trial prematurely,
because this can prolong the weaning process.
Complications
Many complications can occur and vigilance must be constant
when caring for patients on mechanical ventilation.
Complications include, but are not limited to, the following:
Barotrauma (volutrauma)pneumothorax (with and without tension), pneumomediastinum, pneumoperitoneum,
pneumoretroperitoneum, SQ emphysema
Machine failure, alarm failure, ventilator asynchrony, bacterial contamination
Endotracheal tube migration or rupture, vocal cord granuloma, self-extubation, cuff rupture
Nasotracheal intubation associated with nasal necrosis
and sinusitis
Hyperventilation, alveolar hypoventilation, ventilatorassociated pneumonia, tracheoesophageal fistula, hypotension and decreased cardiac output associated with PEEP
and intrinsic PEEP resulting in vascular insufficiency
Other Modes of Mechanical Ventilation

High-frequency ventilation
The two most common variations are high-frequency jet
ventilation and high-frequency oscillation.
Both use an extremely small tidal volume (50%-100% of
dead space volume).
High-frequency oscillation is used in the pediatric
population.
Neither variation depends on bulk gas transport for oxygenation or ventilation.
Partial liquid ventilation
Uses perfluorocarbons, which dissolve very large amounts
of oxygen, but readily release it
836
IV THERAPY
May replace absent surfactant and is attractive strategy
for acute respiratory distress syndrome, but is experimental (trials are under way)
Inverse ratio ventilation
Reverses I:E time in an attempt to improve oxygenation by
increasing mean airway pressure.
Normal inspiratory time is one-half to one-third of expiratory time, so with inverse ratio ventilation, this is reversed.
Can be used with volume-control ventilation, however,
pressure-control ventilation used most often
Very uncomfortable, requires sedation or paralysis
Proportional-assist ventilation
Pressure, inspiratory flow rate, and tidal volume are delivered proportional to the patients spontaneous inspiratory
effort.
Only provides for assisted ventilation
NONINVASIVE POSITIVE PRESSURE VENTILATION

Noninvasive positive pressure ventilation (NPPV) refers to
positive pressure ventilation delivered without the use of an
endotracheal tube.
The most obvious advantage is that it avoids many of the
complications that occur during intubation or with the use
of a ventilator.
The most common delivery methods include the following:
Positive pressure ventilators, which provide ventilatory
support through a tight-fitting facemask or other interface, such as a nasal mask.
Type depends on fit and patient preference.
With this type of delivery, a preset airway pressure or
tidal volume is delivered, either with full support or by
assisting spontaneous patient inspiratory efforts.
Exhalation is passive to a preset PEEP or to atmospheric pressure.
In patients with a nasogastric tube, the facemask may be
leaky, but some ventilators, in a pressure-limited
mode, are able to quantitate the amount of leak and
compensate for the amount lost during inspiration. If
837
a volume-limited mode is used, no compensation can be

made for leak, but an increase in tidal volume will allow
for compensation.
Continuous positive airway pressure provides for a constant positive pressure (relative to atmospheric pressure)
to be delivered to the airway during the entire respiratory cycle.
It does not provide for an inspiratory assist; however, it
does reduce the work of breathing by keeping small
airways open (avoiding intrinsic PEEP).
It is commonly used in the treatment of obstructive
sleep apnea.
Indications
Before using NPPV, consideration must be given to the
patients status.
Cooperative
Minimal secretions
Hemodynamically stable
Able to protect airway
Impending endotracheal intubation
Evidence of acute respiratory failure
Indications for this modality are continuing to expand as
physicians become more familiar with the use and capabilities of NPPV. The following list is not exhaustive:
Exacerbations of COPD
Exacerbations of asthma
Pulmonary edema
Do not intubate
Restrictive lung disease
Obesity hypoventilation syndrome
Neuromuscular disease
Acute lung injury
Initial Settings
Virtually any ventilator can be used for NPPV; however,
units designed strictly for NPPV have extremely rapid cycling
times, minimizing patient-ventilator asynchrony.
Generally an inspiratory pressure of 8-10 cm H O and an
2
expiratory pressure, or PEEP, of 2-5 cm H2O are reasonable
initial settings.
838
IV THERAPY
Further adjustments are guided by patient tolerance and arterial blood gas measurements.
When using bilevel positive pressure ventilators, which are
pressure-limited and time- or flow-cycled, the variable settings are referred to as inspiratory positive airway pressure
and expiratory positive airway pressure. Inspiratory positive airway pressure can be patient- or time-triggered.
Weaning
When clinical improvement is observed, NPPV can be discontinued abruptly or reduced gradually, as with pressure-support ventilation, with the patient being monitored closely
for signs of respiratory decompensation and distress, in which
case NPPV is reinstituted.
Patients may remove the mask for eating and conversation and
generally can replace it when feeling dyspneic.
Complications
When NPPV is used in appropriately selected patients, complications generally are minor.
Complications include the following:
Nasal bridge necrosis
Nasal dryness
Corneal irritation or ulceration
Gastric insufflation
Skin rash at points of skin contact with the mask
A small proportion of patients cannot tolerate the mask
because of discomfort or, less commonly, claustrophobia.
Explaining the role of the mask, giving patient encouragement, and selecting different interfaces may obviate
the need for endotracheal intubation.
839
IV THERAPY
NUTRITION SUPPORT IN
HOSPITALIZED PATIENTS
Kurt A. Kennel, M.D.
M. Molly McMahon, M.D.
CLINICAL ASSESSMENT OF NUTRITIONAL STATUS
Malnutrition
Depletion of body protein stores from starvation and/or
severe illness
Assessment combines history, exam, and lab tests to identify malnourished patients or patients at risk for malnutrition
Historyrecent dietary habits (usual diet, supplements,
herbs, and fad diets), presence of anorexia, nausea, vomiting,
dysphagia, or diarrhea, medical illness, surgical procedure,
medications, alcohol, and unintentional weight loss (see
below)
Exammuscle wasting (temporalis muscle, interosseous
muscles, thin extremities), subcutaneous fat loss, dehydration,
and symptoms and signs of vitamin deficiencies
Lab tests
Albumin and prealbumin are negative acute phase proteins that are altered by stress and are not sensitive markers of nutritional status.
Lab assessment should be individualized but usually
includes electrolytes, glucose, CBC, and kidney and liver
function tests. These also are not nutritional markers but
can easily be altered by disease coupled with poor nutrition.
Risk Factors
Unintentional weight loss >5%-10% of usual weight over
3-6 months (use chart or nursing home weights)
Consider weight in relation to fluid status.
Inadequate (<50% of estimated needs) nutrition over previous
2-4 weeks
Special abbreviations used in this chapter: BEE, basal energy expenditure; BMI,
body mass index; HB, Harris-Benedict (equation).
841
Body mass index (BMI) <18.5, wasted appearance, chronic disease, alcohol abuse, eating disorders, elderly or institutionalized patients
DysphagiaIf suspected, keep patient NPO until swallowing is evaluated
ORAL SUPPLEMENTATION
Indications
Able to safely eat but intake inadequate to meet needs
Prescribing
Ask dietitian to clarify food preferences and to initiate calorie and protein record. Involve patient, dietitian, and nurse
in assessment and implementation.
Many varieties of solid and liquid supplements are available. Consult your formulary.
Specialty products are available for certain disease states,
e.g., renal failure.
Consider small frequent meals; liberalize diet.
Add daily multivitamin.
Monitoring
Review intake and output and weight trends and compare
calorie/protein intake with estimated requirements.
Frequent reassessmentIs nutrition support needed?
INDICATIONS FOR NUTRITION SUPPORT (TUBE FEEDING OR PARENTERAL NUTRITION)

Moderate or severe illness
and
>7-10 days of past or anticipated inadequate intake (<50%
of requirements)
Goals of nutrition support
Enhance immune function, organ function, and wound
healing
Improve net protein balance
Prevent sequelae of malnutrition by providing substrates,
electrolytes, vitamins, and minerals
If patient requires nutrition support, first determine route
(enteral or parenteral) and then estimate nutrition and fluid
requirements.
842
IV THERAPY
ESTIMATION OF NUTRITION AND FLUID REQUIREMENTS
Estimation for hospitalized patients is described in Table 1.
Hamwi estimation of lean body weight (useful when feeding
obese patients)
Men: 106 lb for 5 ft + 6 lb per additional inch
Women: 100 lb for 5 ft + 5 lb per additional inch
Estimated Daily Fluid Requirements
Euvolemic patient with normal heart and kidney function
and no unusual losses needs ~30 mL/kg daily.
If high kidney or gastrointestinal tract losses (nasogastric,
diarrhea, drains, fistulas, ostomy), required daily fluid equals
losses + urine output + 500 mL for insensible losses.
Nondextrose crystalloid solutions, rather than parenteral
or enteral nutrition, should be used to replace unusual
gastrointestinal tract or kidney losses that may vary in
amount from day to day.
Table 1. Estimation of Daily Calorie, Protein, and Fat

Requirements in Hospitalized Patients
ICU patient
Protein
Basal calories using the

Harris-Benedict (HB)
equation
1.5 g/kg of body weight
Fat
20%-30% of total calories
Total calories*
Non-ICU patient
HB to HB plus 20%
1.0-1.5 g/kg of body

weight
20%-30% of total
calories
*If patients body mass index is 25 to <30, limit calories to basal estimate; if
it is 30, provide 75% of basal caloric needs (based on the obese weight).
Harris-Benedict (HB) equation for estimating basal energy expenditure
(BEE)
Males: BEE (kcal/day) = 66.5 + 13.8 (weight in kg) + 5 (height in cm)
6.8 (age in years)
Females: BEE (kcal/day) = 655 + 9.6 (weight in kg) + 1.8 (height in cm)
4.7 (age in years)
(Weight is current or dry weight)
The guidelines for protein assume normal liver and kidney function. The
estimated lean body weight is often used in obese patients to estimate protein needs of 1.5 g/kg.
843
Maximally concentrated enteral and parenteral nutrition

formulas are advised for critically ill patients (often receiving extra fluid and blood products) or fluid overloaded
patients.
TUBE FEEDING
Indications
If nutrition support is indicated and patient is not able to
safely meet nutritional needs by mouth and gastrointestinal
tract is functioning
Examplesstroke and dysphagia; amyotrophic lateral sclerosis and dysphagia
Prescribing
Tubes
For short-term use (<30 days), nasoenteric tubes with tip in
stomach, duodenum, or jejunum are recommended; 12F
diameter tubes are preferred.
Flexible, small diameter feeding tube with a weighted tip
is preferred.
Semirigid nasogastric tube initially placed for decompression is suitable only for short-term use.
Gastrostomy or jejunostomy tube (endoscopic, surgical, or
radiologic)
If anticipated need >4 weeks and
If ethical and acceptable by patient or guardian
Placement of nasoenteric tubes
Bedside or with fluoroscopic or endoscopic assistance
Position of tip must be confirmed radiographically
before use.
Reconfirm position if any question of tube migration.
Prepyloric vs. Postpyloric Tubes
Prepyloric (preferred) allows intermittent feeding (more
physiologic), does not require a pump, and there is more
information about drug absorption with gastric delivery.
Postpyloric feedings should be considered if tube-feedingrelated aspiration, elevation of head of bed >30 is contraindicated, or gastrointestinal dysmotility intolerant of
gastric feeding. All postpyloric tubes must use continuous
feeding program.
844
IV THERAPY
Baseline Lab Tests
Glucose, sodium, potassium, chloride, bicarbonate, BUN/creatinine, AST, albumin, calcium, magnesium, and phosphorus
Other tests individualized to patient
Formulas
Determine estimated need for calories, protein, and fluid.
We include protein in caloric estimate because amino acids
are oxidized and provide energy.
Standard formulas (appropriate for most patients) contain
about 1 kcal/mL, 40 g/L protein, 40 mEq/L sodium, 40
mEq/L potassium, and 300 mOsm/kg water (isosmolar).
Typically, 1,200-1,500 mL formula provides 100% of recommended daily intake of vitamins and minerals.
If feeding <1,500 mL, check formula label and add daily
multivitamin if necessary.
One can of formula ~250 mL
Isotonic feedings are generally administered full-strength.
The exception is infusion of hypertonic (>400 mOsm/L)
feeding into small bowel.
Intermittent (Gravity) vs. Continuous (Pump-Controlled)

Standard progression for continuous tube feeding
Begin with 20 mL/hour and increase by 10-20mL/hour
increments every 12-24 hours to the goal rate.
For intermittent (gravity) feeding
Start 1/2 can over 60-90 minutes with each feeding the
first day of feeding and increase each feeding daily by
1/2 can increment until goal is reached (maximum 2 cans
at any feeding).
Tube patency requires flushing the tube with at least 30 mL
water every 6 hours (more if necessary to meet fluid requirements, see below).
Medications and Tube Feeding

Medications in liquid form are preferred.
Opened capsules and crushed or ground tablets are mixed
with 10-15 mL water and flushed through tube.
845
Extended release and enteric-coated medications should

not be used.
Multiple medications should not be mixed together.
Water is flushed through the tube before and after the administration of medications.
Generally, medications should not be added to the tube feeding formula.
Be aware of
Drugs with high osmolality or sorbitol content, such as
potassium chloride, acetaminophen, and theophylline
Drugs that clog tubes, such as psyllium, ciprofloxacin
suspension, sevelamer, and potassium chloride (do not
use potassium chloride tablets, use liquid or powder form)
Drugs whose absorption is interfered with by tube feeds,
such as phenytoin
Consult with a pharmacist about tube feeding and medication
issues.
Consult nutrition team or dietitian for use of specialty formulas or if patient will be dismissed home on tube feedings
for assistance with nutrition program, supplies, insurance,
and follow-up.
Example
A 66-year-old man unable to eat because of dysphagia after
a stroke. Gastrointestinal tract is functioning. He is not in
ICU. Height is 168 cm, weight is 60 kg, and BMI is 21.
HB (male) = 66.5 + 13.7 (60) + 5 (168) 6.8 (66), so BEE
= 1,280 kcal/day
Calorie goalHB plus 20% is ~1,500 kcal/day.
Protein goal1 g/kg daily = 60 g/day
Estimated fluid requirement30 mL/kg daily 60 mg =
1,800 mL/day
Therefore, standard formula with 1.0 kcal/mL and 44 g protein/L would require 1,500 mL/day to provide 1,500 kcal/day
(HB + 20%), 66 g protein (1.1 g/kg daily), and adequate
vitamins
1,800 mL 1,500 mL in tube feeding formula = 300
mL/day fluid still required
Continuous Feeding Program (Requires Pump)

1,800 mL/24 hours = 75 mL/hour
846
IV THERAPY
300 mL fluid still needed divided 4 per day = 75 mL of

water tube flush every 6 hours
Intermittent Feeding (Gravity) Program

One can standard formula is ~250 mL, so ~250 kcal/can.
Two cans (AM), 2 cans (midday), 2 cans (early evening) =
1,500 kcal/day and 1,500 mL/day fluid
300 mL fluid is still needed because six flushes (before and
after each feeding) = 50 mL per flush
Monitoring
Check residuals of feeding tube.
For prepyloric feeding, the residual fluid should be <100
mL, otherwise hold feeding for 1 hour and recheck.
If residual remains increased, check for abdominal distension and tube placement.
For postpyloric feeding, the residual fluid should be monitored to rule out tip migration back into the stomach.
Is patient tolerating feeding? Check for abdominal distension or pain, diarrhea, or constipation.
Intake and output, daily weights, lab tests (see below),
increase >0.25 kg/day should be attributed to fluid gain
1-1.5 L of urine output is generally adequate.
Frequent reassessmentIs more or less nutrition support
needed? Is fluid still appropriate?
Complications
Diarrheacommon problem but might not be caused by
tube feeding
Review medications for sorbitol (in liquid medicines),
magnesium, and osmolality.
Consider an infectious cause (especially Clostridium
difficile).
Rule out infusion of full-strength hyperosmolar formula
or medications into jejunum.
Can try fiber-containing formula and, if no infection, loperamide or tincture of opium.
Abdominal distension or pain
847
Assess for ileus, obstruction, or other abdominal lesion.

Stop the tube feeding until problem has been resolved,
then restart slowly.
Constipation
Be certain fluid (including water program) is adequate.
Fiber-containing formula can be used.
Aspiration
Elevate the head of the bed 30- 45 during feeding.
Check residual volumes every 6 hours if continuous program or before feeding if intermittent program.
Consider postpyloric placement (see above).
Recheck tube placement by X-ray after placement or
manipulation.
Metabolic abnormalities
HypernatremiaEnsure adequate volume.
HyperglycemiaMonitor glucose and treat as appropriate.
Tube-relatedsinusitis, clogged tube, and tract infection
Refeeding syndrome (see below)
PARENTERAL NUTRITIONDEXTROSE, PROTEIN, FAT,

ELECTROLYTES, VITAMINS, AND MINERALS
Indications
If nutrition support is indicated and gut cannot be used (i.e.,
ileus, distal bowel obstruction, short-gut syndrome/malabsorption, or severe dysmotilityif tube feeding is not
tolerated)
Prescribing
Determine estimated need for daily calories (carbohydrate,
protein, fat) and fluid.
We include protein in caloric estimate because amino acids
are oxidized and provide energy.
Recall that a 10% solution = 10 g/dL = 100 g/L, i.e., 10% dextrose = 100 g/L (3.4 kcal/g dextrose), 5% amino acid = 50 g/L
(4 kcal/g protein), 10% fat emulsion = 1.1 kcal/mL, and 20%
fat emulsion = 2 kcal/mL.
Central access, central parenteral nutritionConfirm catheter
tip is in superior vena cava by chest X-ray before initiating
Peripheral access; peripheral parenteral nutrition
Peripheral parenteral nutrition may be used if the patient
848
IV THERAPY
is mildly to moderately stressed and requires short-term

Infrequently used because 1 L provides few calories and
large volumes are required to meet nutrition needs
Osmolarity should be <900 mOsm/L and is estimated as
follows:
% amino acids 100 + % dextrose 50 + Na (mEq/L)
2 + K (mEq/L) 2 + 25
Baseline lab valuesglucose, sodium, potassium, chloride,
bicarbonate, BUN/creatinine, AST, albumin, calcium, magnesium, and phosphorus
Other tests individualized to the patient
Check triglycerides if patient has pancreatitis, is taking propofol, has a history of hypertriglyceridemia or poorly controlled diabetes.
If >400 mg/dL, stop or reduce fat emulsion.
Parenteral nutrition can help correct chronic metabolic abnormalities but should not be used as the sole treatment for acute
metabolic abnormalities, e.g., electrolyte, mineral, or acidbase disorders.
Some drugs can be added to parenteral nutrition, especially
if fluid restriction is needed (ask pharmacist).
If patient will be dismissed home on parenteral nutrition,
consult nutrition team for assistance with patient selection,
catheter selection and placement, outpatient nutrition program, monitoring, reimbursement, and insurance issues.
Example
A 54-year-old woman is unable to eat because of ileus due
to abdominal abscess and sepsis. Features: 15% recent
weight loss, is in ICU, is euvolemic, height is 172 cm, weight
is 53 kg, estimated lean weight is 53 kg, and BMI 18.
HB (female) = 655 + 9.6 (53) + 1.8 (172) 4.7 (54), so BEE
= 1,220 kcal/day
Caloric goalHB = 1,228 kcal/day
Protein goal1.5 g/kg daily = 1.5 g 53 kg = 80 g protein/day
Fat goal20%-30% calories from fat
849
Estimated fluid requirement30 mL 53 kg = 1,590 mL/day

Distributing the calories among macronutrients
Protein80 g 4 kcal/g = 320 kcal
Fat250 mL of 10% fat emulsion = 275 kcal (22% of
total kcal)
Dextroseneed additional 633 kcal from dextrose to meet
BEE requirement
633 kcal/3.4 kcal/g of dextrose = 186 g dextrose
Nonfluid-restricted formula
1,590 mL/day total 250 mL of fat = 1,340 mL for amino
acids and dextrose
80 g amino acids in 1,340 mL requires 80 g/13.4 dL =
6% amino acid solution
186 g dextrose in 1,340 mL requires 186 g/13.4 dL = 14%
dextrose solution
Therefore, formula would be 1,340 mL of 14% dextrose
and 6% amino acid + 250 mL of 10% fat emulsion to provide 1,228 kcal (HB), 80 g protein (1.5 g/kg daily), and
22% of kcal from fat. Infuse over 24 hours, so 1,340
mL/24 = 56 mL/hour.
Fluid-restricted (maximally concentrated) formula
80 g protein from 10% amino acid source (100 g amino
acid/L) requires 800 mL
186 g dextrose from 70% dextrose (D70, 700 g dextrose/L)
requires 266 mL
Thus, 1,066 mL is minimal fluid needed for dextrose and
amino acids.
Therefore, formula would be 1,066 mL of 17% dextrose
and 7.5% amino acid + 250 mL of 20% fat emulsion to provide 1,228 kcal (HB), 80 g protein (1.5 g/kg daily), and
22% kcal from fat.
1,066 mL/24 hours = 45 mL/hour
Monitoring
Chest X-ray to confirm position of catheter tip
Daily intake and output and weightIncrease in excess of
0.25 kg/day should be attributed to fluid gain.
Daily heart and lung exam, assessment of fluid status
Catheter site for infectionalways suspect if fever
Glucose after initiation of parenteral nutrition
Aim for 80-120 mg/dL in critically ill patients with
850
IV THERAPY
hyperglycemia. Given that there is limited information

for glucose goals for stable patients on wards and tight
glucose control is difficult to achieve safely with SQ insulin
programs in hospitalized patients, a goal range of 100150 mg/dL is reasonable for patients on wards.
If above is the goal, regular insulin can be added to
parenteral nutrition starting with 0.1 U per gram dextrose
and increasing up to 0.2 U per gram dextrose in parenteral
nutrition.
Some patients will also require SQ insulin or graded insulin
infusion.
Check sodium, potassium, and glucose daily to start, other
tests and frequency should be individualized.
Check for added calories such as dextrose or propofol (formulated in 10% fat emulsion, provides 1.1 kcal/mL). Fat
emulsion may need to be reduced or discontinued if patient
takes propofol.
Frequent reassessmentIs more or less nutrition support
needed? Is volume still appropriate? Can program be converted to tube feeding?
Complications
Central line-relatedmalposition, pneumothorax, infection,
thrombosis, and bleeding
Overfeeding can cause hyperglycemia, abnormal liver tests,
and increased carbon dioxide production.
Metabolic abnormalitiesacid-base and electrolytes, hyperglycemia
Refeeding syndrome can occur when severely malnourished patients are aggressively refed. Complications
typically occur within first 5 days of feeding and include
hypokalemia, hypophosphatemia, fluid overload, and cardiac
arrhythmias.
Check and replace potassium, phosphorus, and magnesium in patients at risk before initiating nutrition support.
Avoid overfeeding. Begin with basal (using current, not
ideal, weight) calorie requirement, watch fluid balance,
monitor and replace electrolytes, and give thiamine.
851
IV THERAPY
OXYGEN THERAPY
Apoor S. Gami, M.D.
Jeffrey T. Rabatin, M.D.
CLASSIFICATION
Delivery Devices
Oxygen delivery devices are described in Table 1.
Oxygen flow and expected fraction of inspired oxygen (FIO )
2
for different delivery devices are listed in Table 2.
Indications
Indications for low-flow and high-flow devices are listed in
Table 3.
Acute myocardial infarction and congestive heart failure
For hypoxemia due to left ventricular failure, pulmonary
edema, ventilation-perfusion mismatch
Does not increase oxygen delivery if patient is not hypoxemic
May increase systemic vascular resistance and decrease
cardiac output slightly.
Can be omitted if PaO2 is normal
No effect on complications or survival
Acute cor pulmonale
Rapid and dramatic improvement of pulmonary hemodynamics
Decreases right ventricular afterload with pulmonary
infarction, infection, COPD
Chronic cor pulmonale
Criteria for chronic oxygen therapy
PaO2 <55 mm Hg or SaO2 88%
Or in the presence of cor pulmonale, heart failure, or
erythrocytosis (hematocrit >55%), PaO2 56-59 mm Hg
or SaO2 89%
Special abbreviations used in this chapter: A-a, alveolar-arterial; ABG, arterial
blood gas; FIO2, fraction of inspired oxygen; SaO2, arterial oxygen saturation.
853
Table 1. Oxygen Delivery Devices

Type
Low-flow
High-flow
Delilvery device
Nasal cannula
Simple face mask
Partial rebreather mask
(reservoir)
Othersnasal catheter,
transtracheal catheter
Non-rebreather mask
(reservoir + 1-way
valve)
Venturi mask
Downs Flow Generator*
Notes
FIO2 variable dependent on:
Minute volume (RR
tidal volume)
Inspiratory flow rate
FIO2 more precise

Oxygen delivery >4
patients minute volume
Larger oxygen reservior
FIO2, fraction of inspired oxygen; RR, respiratory rate.

*Vital Signs, Inc., Totowa, New Jersey.
Or in the presence of lung disease or other clinical

needs, PaO2 60 mm Hg or SaO2 90%
Oxygen therapy should be prescribed for daytime and
nighttime (and appropriately titrated) if these criteria are
met during the day
Oxygen therapy should be prescribed for exercise or sleep
if these criteria are met during that activity
Order sufficient oxygen to achieve PaO2 >60 mm Hg.
Note: Oxygen therapy is the only treatment that improves
survival in COPD.
Air travel
Patients who require oxygen therapy at sea level will
require it when traveling by airplane.
Patients are not allowed to carry their own oxygen supply aboard a commercial airplane. Patients must notify the airline of their oxygen need, and they must carry
a detailed oxygen prescription. Airlines usually require
48 hours to arrange for in-flight oxygen.
Hypoxemia
Is due to many conditionsinterstitial lung disease, pulmonary fibrosis, acute respiratory distress syndrome, asthma, pulmonary embolism, pneumonia, pneumothorax,
laryngeal infections, sickle cell crisis, anaphylaxis, circulatory shock
854
IV THERAPY
Table 2. Delivery Devices, Oxygen Flow, and Expected FIO2
Device
Nasal cannula
Simple face mask

Partial rebreather
Non-rebreather
Venturi mask
Downs Flow Generator*
100% O2 flow, L/minute

1
2
3
4
5
6
7
8
5-7
8-10
6
7
8-15
15-flush ( 60)
Usually >40
80-100
FIO2, %
24
28
32
36
40
44
48
52
40-50
50-60
50
65
80
90+
Up to 50
Room air-100
FIO2, fraction of inspired oxygen.

*Vital Signs, Inc., Totowa, New Jersey.
Goal
Maintain PaO2 >60 mm Hg or SaO2 >90%
PaO2 levels >80 mm Hg are rarely necessary.
Oxygen is the definitive treatment.
Hyperbaric oxygen treatments may reduce long-term complications, but there is no consensus about the best dose and
schedule. Administration of 3 treatments within 24 hours
showed benefit in one trial.
Order 100% FIO2 by a non-rebreather mask at 10 L/minute
until carbon monoxide levels are <10% and all symptoms
and any cardiovascular or central nervous system instability
resolve.
Infants and pregnant women require treatment hours
after symptoms resolve because of predominance of fetal
hemoglobin, which has a higher affinity for carbon
monoxide.
855
Table 3. Indications for Low-Flow and High-Flow Devices

Device
Low-flow
High-flow
Indications
Short-term therapy (e.g., postoperatively)
Long-term therapy (e.g., chronic hypoxemia)
Temporizing measure
Temporizing measure before assisted ventilation
becomes necessary
Cluster headaches
Oxygen is the most effective treatment for an acute attack.
Order 100% FIO2 for 15 minutes.
Gas gangreneHyperbaric oxygen therapy is controversial.
Obstructive sleep apneaNocturnal oxygen alone is not
effective.
Important points
Cyanosis is not an accurate indicator of PaO2 (many falsepositive and false-negative results).
Compromised brain function at PaO2 55 mm Hg
Loss of consciousness at PaO2 30 mm Hg
Monitoring
Arterial blood gas (ABG) measurements
Routine ABG monitoring is misleading because of poor
precision.
Inconsistent with repeated measurements: variation = 13
18 mm Hg.
A PaO2 change on a routine ABG is not necessarily
abnormal if the patients clinical status has not changed.
Advantage
Wealth of other information about clinical status
Useful when clinical status deteriorates and pulse oximetry waveform is unreliable.
Important points
The alveolar-arterial (A-a) PO2 gradient is affected by oxygen therapyThe normal A-a PO2 gradient increases 5-7
mm Hg for every 10% increase in FIO2 (because of loss of
regional hypoxic vasoconstriction in poorly ventilated
lung regions).
Pulse oximetry
856
IV THERAPY
Advantages
Excellent accuracy, superior precision
High sensitivity for detection of hypoxic episodes
Inexpensive, noninvasive, and free of complications
Limitations
Accuracy within 3% (when SaO2 >70%)
Overestimates
Elevated methemoglobin (high-dose nitroglycerin)
Elevated carboxyhemoglobin (smoke inhalation)
Underestimates
Hypotensionaccurate down to blood pressure of
30 mm Hg
Anemiaaccurate down to hemoglobin 3 g/dL
Nail polish
Jaundice and skin pigmentation
Hypothermia, motion artifact
Important points
Ear probes have faster response times than finger probes.
Check pulse oximetry or ABG 20 minutes after changing patients FIO2.
Continuous pulse oximetry typically is only for ICU or
unstable patients.
Always check different sites and waveforms before making therapeutic decisions.
Prescribing
Low-flow devices
FIO2 depends on the patients minute volume and inspiratory flow rate.
If large tidal volumes or tachypnea, FIO2 is lower than
estimates in Table 2.
Good initial choice for patient who is hemodynamically
stable but mildly hypoxemic
High-flow devices
They provide the total inspiratory volume at predictable
FIO2 levels.
Prescribe for those who need consistent FIO2 and have
varying tidal volumes and respiratory rates.
857
Important points
With nasal cannula, FIO2 generally does not vary with
mouth vs. nose breathing.
Order therapy early because it may take time to obtain
the next needed device.
COPD
ProblemVentilatory drive is PaO2-dependent in a small
percentage of patients with COPD.
If patient is hypoxic, aggressive oxygen therapy can
decrease the respiratory rate, leading to progressive
hypoxemia and respiratory acidosis.
Goalmaintain adequate PaO2 while limiting hypercapnia
Withholding oxygen therapy may be harmful.
If oxygenation is inadequate and/or patient has progressive
hypercapnia, initiate assisted ventilation (i.e., Ambu-bag,
noninvasive mechanical ventilation, intubation and
mechanical ventilation).
Important point
Pediatric flow meters accurately measure oxygen flow
from 0.25 to 3.0 L/minute. If these are available, titrate
flow in 0.25-L/minute increments in patients with
COPD.
Complications
Nasal cannula
Mucosal irritation, drying, and bleeding
Especially with flow rates >4 L/minute and nonhumidified
oxygen
Masks
Aspiration, emesis traps
Because of difficulty eating and drinking, there is risk of
acute hypoxemia with noncompliance.
Venturi one-way valve may stick because of moisture.
Important points
Order a humidifier or nebulizer to increase the water content of inspired gases.
Order the lowest flow rate necessary to achieve the goals
of therapy.
Complications
Progressive symptoms of oxygen toxicity include
858
IV THERAPY
Substernal discomfort or pain

Cough
Deeper breathing, worsening cough and pain
Decreased vital capacity
Complications of toxic oxygen therapy are listed in Table 4.
Reasonable limits of toxic FIO2 therapy are listed in Table 5.
Important points
The shunt fraction determines the effect of FIO2 on
PaO2.
When shunt fraction is >50%, PaO2 is essentially independent of changes in FIO2.
Thus, with high shunt fractions (acute respiratory distress syndrome), FIO2 can be lowered to nontoxic levels.
Table 4. Clinical Complications of Toxic Oxygen Therapy

Time breathing toxic FIO2
12 hours to days
Days to 1 week
>1 week
Clinical complications
Tracheobronchitis
Decreased vital capacity
Interstitial pulmonary edema
Pulmonary fibrosis
Table 5. Reasonable Limits of Toxic FIO2 Therapy

FIO2, %
Time, hours
100
80
60
50
12
24
36
Unlimited*

*Even nontoxic levels of FIO2 have potential to cause complications listed
in Table 4, especially in more debilitated patients. Some have advocated
supplementing antioxidants (e.g., selenium) for these patients to prevent
complications of oxygen therapy, but no evidence supports this.
859
IV THERAPY
PAIN MANAGEMENT
K. L. Venkatachalam, M.D.
Paul E. Carns, M.D.
PAIN CONTROL
Three approaches to controlling pain are as follows:
Modify the source of pain.
Alter the central perception and spinal cord modification
of pain.
Block the transmission of pain to the central nervous system.
Treat pain aggressively and quickly to provide the patient
sustained relief.
DEFINITIONS
Tolerancecondition in which a larger dose of opioid analgesic is required to maintain the original effect (a common
occurrence in chronic users)
Dependencephysical condition in which the abrupt
discontinuation of an opioid (after chronic use) or the administration of an opioid antagonist produces an abstinence
syndrome (anxiety, irritability, chills, hot flashes, salivation,
lacrimation, rhinorrhea)
Addictionpsychologic condition defined as a pattern of
compulsive drug use characterized by a continued craving for
an opioid and the need to use opioids for effects other than
pain relief
Pseudoaddictioniatrogenic condition resembling addiction due to opioid doses that are too low or spaced too far apart
to relieve pain
INDICATIONS
Obtain a thorough pain history.
Use the mnemonic OLD CARTSonset, location,
Special abbreviation used in this chapter: PCA, patient-controlled analgesia.

861
duration, characteristic, aggravating factors, relieving

factors, treatments, and severity.
Ascertain and verify pain intensity frequently from the
patient by using a reliable verbal or numerical scale.
Mild pain1-4
Moderate pain5-6
Severe pain7-10
Perform a thorough physical exam, probing for tender points
of inflammation or muscle spasm.
It is important to arrive at the correct diagnosis.
Treat pain during the diagnostic work-up, but do not miss
treatable underlying causes, e.g., pulmonary embolism,
acute abdomen, radiculopathic pain with progressive
neurologic deficit.
The World Health Organization recommends the use of a
Three-Step Analgesic Ladder to guide therapy:
Treat mild-moderate pain with nonopioid analgesics
(step 1).
Maximize the dose of the nonopioid analgesic, and add a
step 2 opioid analgesic if the pain is mild-moderate despite
the use of nonopioid analgesics. Increase the dose for
patients with moderate-severe pain despite step 2 opioids.
If this is not feasible, use a step 3 opioid.
CLASSIFICATION OF THERAPY
The various classes of therapy and the corresponding medications and indications are outlined in Table 1.
Note that all prescribing information is based on adult dosages.
If possible, start with PO analgesics because they are the
preferred form.
Avoid IM injections.
When administering IV medication, patient-controlled
analgesia (PCA) is the preferred mode of delivery.
THE GIST OF PCA

The following adjustments may be made to a PCA machine
(Table 2):
IV drug bolus dose per patient request
Lockout intervaltime following bolus dose during which
the PCA machine will not dispense any medication despite
patient requests
862
IV THERAPY
Table 1. Classes of Therapy, Representative Medications,
and General Indications
Class of therapy
Nonopioid
analgesics
Opioid analgesics
Analgesic
adjuvants
Representative
medications
Acetaminophen
Aspirin
Choline magnesium
trisalicylate
NSAIDs (many
classes)
Tramadol (both
opioid & nonopioid)
Codeine
Dihydrocodeine
Hydrocodone
Oxycodone
Morphine
Hydromorphone
Fentanyl
Tricyclic antidepressants
Benzodiazepines
Caffeine
Corticosteroids
Anticonvulsants
General indications
Good baseline control
of mild-moderate
pain
Step 2 opioids for

moderate pain
despite nonopioids
Step 3 opioids for
severe pain despite
step 2 opioids
Used to enhance
effects of analgesics
or counteract their
side effects
Maximum doseset so that the patient may receive medication only 10 times per 4 hours.
Patients can request it as much as they want but will
be locked out.
Baseline infusionnot always required but useful if patient
is trying to sleep or is unable to operate PCA machine
Equianalgesic opioid conversion factors (Table 3)
Equianalgesic dose of transdermal fentanyl to morphine
(Table 4)
Conversion of IV morphine to sustained-release morphine
Total the daily requirement of immediate-release morphine
(IV and PCA) and convert to PO dosage. Next, convert
to the nearest equivalent of sustained-release morphine,
863
864
Table 2. Patient-Controlled Analgesia Dosage

Drug concentration
Bolus dose
Lockout interval,
minutes
Maximum dose,
per 4 hours
Baseline infusion,
per hour
Morphine (MSIR)
(1 mg/mL)
Fentanyl (10 g/mL)
Hydromorphone
(0.2 mg/mL)
1-5 mg
5-20
10-50 mg
1-10 mg
15-50 g
0.1-0.5 mg
3-10
5-15
150-500 g
1-5 mg
20-100 g
0.2-0.5 mg
Data from Mayo Clinic Anesthesia Department Inpatient Pain Service Guidelines.
IV THERAPY
Table 3. Equianalgesic Opioid Conversion Factors*
Opioid
Codeine
Fentanyl
Hydrocodone
Hydromorphone
Meperidine
Morphine
Oxycodone
IM/IV
PO, mg
-100 g
-1.5 mg
75 mg
10 mg
--
200
-5-10
7.5
300
30
20
*Note that these are not recommended doses but only conversion factors.
Table 4. Transdermal Fentanyl to Morphine Conversion

Transdermal fentanyl,
g/hour
Morphine PO,
mg/24 hours
Morphine IV,
mg/24 hours
25
50
75
100
30-90
91-150
151-210
211-270
10-30
31-50
51-70
71-90
Modified from Donner B, Zenz M, Tryba M, Strumpf M. Direct conversion

from oral morphine to transdermal fentanyl: a multicenter study in patients
with cancer pain. Pain. 1996;64:527-34. Used with permission.
e.g., PCA2 mg/bolus dose, 10-minute lockout, 30 mg

maximum per 4 hours. Actual 24-hour usage found to be
60 mg IV. (Check PCA machine for specific daily usage.)
Convert to PO dosage using the equianalgesic opioid conversion factors chart (Table 3).
60 mg IV morphine = 180 mg PO morphine (1:3 conversion)
Use long-acting morphine sulfate 90 mg PO every 12 hours
or 60 mg PO every 8 hours (180 mg/day) plus 15-30 mg
MSIR PO every 4 hours as needed for breakthrough pain.
PAIN PEARLS AND PITFALLS

Always believe the patient.
Be mindful of the patients baseline analgesic use, because
865
he or she may have developed tolerance. Adjust dosages

accordingly.
Patients may need initial boluses of opioid before IV PCA is
started.
Acetaminophen and ibuprofen can provide excellent baseline
control of pain as long as they are used on a scheduled basis
(Tables 5 and 6).
Always provide constipation prophylaxis when using opioid
(Table 7).
If the duration of analgesia is insufficient or decreases with
time, increase the magnitude of each dose, not the dosing
frequency.
Morphine can provide pain relief without interfering with
the patients ability to give consent or the physicians ability to make a diagnosis (Table 5).
The incidence of addiction in patients with pain is low and
not affected by opioid administration by health care providers.
Administer analgesics regularly (not just as needed) if pain
is present most of the time.
With the elderly, start low and go slow. Initial doses should
be 25%-50% lower than for young adults.
Do not use placebos to assess pain.
866
Table 5. Symptom-Oriented Prescribing Information and Adult Dosages for Acute Pain
Condition
Headache (severe tension or migraine)
Unresponsive migraine
Odynophagia (from oral infections or

irradiation)
Ibuprofen 600 mg PO tid

Add acetaminophen 1 g PO qid
If refractory, ketorolac 30 mg IV or 60 mg IM
Sumatriptan 25 mg PO/6 mg SQ; increase PO dose to 50 mg every 2 hours
(300 mg max/day); repeat SQ dose in 1 hour (12 mg max/day)
Rizatriptan (Maxalt, Maxalt MLT) 5-10 mg PO, may repeat in 2 hours
(max dose, 30 mg/24 hours); Maxalt MLT tablets dissolve under tongue
Adjunctive therapy with metoclopramide 10 mg IV or prochlorperazine
10 mg IV/25 mg PR
Caffeine 100 mg PO every 4-6 hours
Dihydroergotamine (DHE, migranal) 1 mg IV, IM, or SQ; may repeat once
Gabapentin started at 300 mg PO at bedtime, increasing by 300 mg every
3 days to a goal of 600 mg tid over 15 days; this may be increased further
depending on patient response to a max of 3,600 mg/day
Carbamazepine 200-400 mg PO qid
Haddads solution (2% viscous lidocaine 10 mL, Maalox 10 mL,
diphenhydramine elixir 10 mL) swished & swallowed every 6 hours
867
IV THERAPY
Treatment
868
Table 5 (continued)
Condition
Costochondritis
Dyspepsia
Angina pectoris
Unstable angina
Abdominal pain
Pelvic pain
Treatment
If ulcer history or gastrointestinal distress, rofecoxib 25 mg PO daily (short term use
only)
Ketorolac 30 mg IV/IM for immediate relief
GI cocktail (Maalox or Mylanta 30 mL, 2% viscous lidocaine 10 mL, and
Donnatal 10 mL) PO; repeat once in 2-4 hours
For long-term relief, pantoprazole 40 mg PO daily or lansoprazole 30 mg PO daily
For stable angina, nitroglycerin 0.4-mg tablets SL or 1 spray under tongue every 5
minutes to max of 3 doses; for prophylaxis, isosorbide dinitrate 40-80 mg PO bid
Nitroglycerin IV bolus 12.5-25 g, then 10-20 g/minute; titrate to effect
If refractory and patient agitated, morphine sulfate 1-3 mg slow IV every 10 minutes
If severe enough to merit analgesics, morphine sulfate 2-4 mg IV every 15 minutes
(will not interfere with patients ability to give informed consent or physicians
ability to make diagnosis)
Alternatively, morphine sulfate PCA2-4 mg/dose, 10-minute lockout, 20-40 mg
max every 4 hours
Table 5 (continued)
Condition
Pelvic pain (continued)
Renal colic
Vaso-occlusive crisis
Treatment
For breakthrough pain, acetaminophen with codeine (300 mg/30 mg) 1-2
tablets every 4 hours (do not exceed 4 g/day total of acetaminophen)
Oxycodone 5-10 mg PO every 6 hours
Tramadol 50-100 mg PO every 4-6 hours to 400 mg max/day
Meperidine 50-100 mg PO every 4-6 hours (do not use for more than 48
hours)
Ketorolac 15-30 mg IM/IV or indomethacin 100 mg PR initially
If refractory, morphine sulfate PCA2-4 mg/dose, 10-minute lockout,
20-40 mg max every 4 hours
Aggressive control required; morphine sulfate IV or PCAbaseline
infusion 1-10 mg/hour, 2-4 mg/dose, 10-minute lockout, 40-80 mg max
every 4 hours
869
IV THERAPY
bid, twice daily; PCA, patient-controlled analgesia; PR, per rectum; qid, 4 times daily; SL, sublingual; tid, 3 times daily.
870
Table 6. Symptom-Oriented Prescribing Information and Adult Doses for Chronic Pain
Condition
Cancer pain (may be somatic, visceral,
or neuropathic pain)
Cancer pain with dysphagia
Treatment
For mild-moderate pain, ibuprofen 600 mg PO tid with acetaminophen 1 g PO qid
If intolerant of ibuprofen, replace with rofecoxib up to 50 mg PO daily (short term use
only)
For continued pain, oxycodone 5-10 mg PO every 6 hours prn or 30-60 mg of codeine
every 4-6 hours prn
If refractory, add morphine sulfate, immediate release (MSIR) 15-30 mg PO every 4
hours & determine effective daily dose; replace with equivalent dose of sustainedrelease morphine bid (see Table 3) with MSIR for breakthrough pain
(the maximum dose of morphine under these conditions is determined only by
the degree of pain control & side effects)
Morphine elixir or rectal suppositories (except for patients with bone marrow
suppression) in equivalent doses; alternatively, transdermal fentanyl (see Table 4);
replace transdermal fentanyl every 72 hours; slightly higher serum levels may be
achieved by replacing fentanyl every 48 hours; continue other pain medications for at
least 24 hours until transdermal fentanyl takes effect; fentanyl transmucosal lozenges
in equivalent doses may also be used
Morphine PCA2-4 mg/dose, 10-minute lockout, 20-40 mg max every 4 hours
Fentanyl PCAbaseline infusion 20-100 g/hour, 15-50 g/dose, 3-10minute
lockout, 150-500 g/4 hours
Table 6 (continued)
Condition
Adjuvant therapy for neural plexus
malignancy
Metastatic bone pain
Joint pain
Bursitis
Treatment
Dexamethasone 16 mg/day
Pamidronate IV 90 mg over 2 hours every 4 weeks
Acetaminophen 1 g PO qid & ibuprofen 600 mg PO tid
For ibuprofen intolerance, rofecoxib 25 mg PO daily
Codeine/acetaminophen (30 mg/300 mg) every 4-6 hours for moderatesevere pain
Betamethasone + 1% lidocaine (specific volumes for each bursa)
intrabursal injection
PCA, patient-controlled analgesia; prn, as needed; qid, 4 times daily; tid, 3 times daily.
IV THERAPY
871
872
Table 7. Drug Complications and Contraindications

Medication
NSAIDs
Acetaminophen
Aspirin
Carbamazepine
Gabapentin
Haddads solution
GI cocktail
Nitroglycerin
Morphine
Complications and contraindications

Dyspepsia, ulcers, gastrointestinal tract perforation, colitis, renal insufficiency, prolonged PT & bleeding
Over-anticoagulation with warfarin; severe hepatotoxicity in alcoholics & patients with liver disease
Do not use more than 4 g/day in nonalcoholics with normal liver function
Gastritis, gastric bleeding; associated with Reye syndrome in children <12 years
Aspirin hypersensitivity with rhinitis or asthma or more serious combination of angioedema, hypotension
& urticaria may occur
Aplastic anemia & liver function abnormalities; monitor serial CBCs & liver function tests for prolonged use
Sedation, ataxia, nystagmus, SIADH
Sedation, ataxia, & nystagmus
Dose reduction needed in renal failure
Marked reduction in gag reflex (do not give near meal times)
Avoid in renal failure
Contraindicated with hypotension, severe bradycardia or tachycardia, right ventricular infarction, & sildenafil
use within 24 hours
Respiratory depression, constipation, hypotension, sedation, nausea, vomiting; change dose or route of drug,
aiming for more constant levels; add medication to counteract side effect
For sedation, caffeine 60-200 mg PO daily
For constipation, prophylaxis with docusate sodium, 100 mg PO bid with senna 2-6 tablets PO bid (goal of 1-2
soft bowel movements/day); lactulose, laxative suppositories, & magnesium citrate to relieve constipation
Table 7 (continued)
Medication
Complications and contraindications
bid, twice daily; SIADH, syndrome of inappropriate antidiuretic hormone.

873
IV THERAPY
Morphine (continued) For mild nausea, prochlorperazine 10 mg IV every 6-8 hours

For severe nausea, ondansetron 4 mg IV every 8 hours
For respiratory depression that needs reversal, use dilute solution of naloxone (0.4 mg in 10 mL
normal saline administered as 0.5 mL IV push every 2 minutes); watch for profound withdrawal,
seizures, & severe pain
Morphine-6-glucuronide is active metabolite with decreased elimination in renal failure, resulting in
enhanced potency & prolonged duration of action
Tramadol
Avoid in opioid-dependent patient
Lowers seizure threshold (avoid in patients with history of seizures or taking antidepressants)
Dose reduction needed in renal insufficiency
Meperidine
Normeperidine, a metabolite, produces anxiety, tremors, myoclonus, & generalized seizures with
repetitive dosing
Avoid in renal insufficiency
Limit use to 48 hours
Do not use for chronic pain
Sumatriptan
Nausea, vomiting, malaise, vertigo, warmth
IV THERAPY
PROCEDURES
Matthew W. Martinez, M.D.
Adam J. Locketz, M.D.
Jon O. Ebbert, M.D., M.Sc.
DOCUMENTATION
Obtain informed consent before the procedure.
The patient or person making medical decisions for the
patient should be clearly informed of the following:
Purpose of the procedure (diagnosis and/or therapy)
Risks of the procedure (bleeding and infection)
Alternative interventions
General procedural technique
Patients, guardians, or power of attorney should be
allowed to ask questions.
Procedural note
Discussed risks, benefits, and alternatives of (insert procedure here) with the patient (and/or guardian/power of
attorney). Patient expressed an understanding of risks,
benefits, and alternatives and asked appropriate questions,
which were answered. Patient agreed to proceed.
Include the following:
Date
Name
Pager
Supervised by (if indicated)
Indication
Brief description of the procedure, including
Amount of anesthetic used
Estimated blood loss
Fluid removed (if any)
Testing performed
Notable hemodynamics (if any monitored)
Complications (if any)
875
ARTHROCENTESIS
All joint procedures require Indications, Contraindications, Suggested Equipment for Joint Aspiration,
and Preparation and Anesthesia (see below).
Specific joints are outlined beginning with Specific Joints.
Indications
Diagnostic indications of arthrocentesis include evaluating
the cause of a joint effusion (including crystal-induced, traumatic, infectious, or inflammatory or degenerative processes).
It is particularly important to rule out a septic joint, which
is perhaps the only rheumatologic emergency.
Therapeutic indications include removing pus from a septic
joint, pain relief from removal of fluid, injection of local
anesthetic, corticosteroid, or visco-supplementation.
Contraindications
Severe coagulopathy
Broken skin or cellulitis over intended entry site
Joint prosthesisshould always be performed by an orthopedic surgeon
Bacteremia or sepsis syndromeThis seems counterintuitive to many residents. You can tap a joint if it is suspected to be infected but the patient is without diagnosed
bacteremia or sepsis.
NoteArthrocentesis can be performed safely with normal
anticoagulation (INR 2-3).
Suggested Equipment for Joint Aspiration

Most hospitals have a prepared Aspiration Tray that can be
ordered.
Bottle of povidone-iodine solution
Alcohol swab
Needles1-inch 25 gauge and a 1.5-inch 25, 20, 18, or 15
gauge (depending on joint injection)
Syringestwo 6 mL, 35 mL (for large knee volumes)
Lidocaine 1% 30 mL
Drape
Sterile gloves
Tubes for culture, Gram stain, cell count, crystal analysis
Disposable pad for placing under the joint
876
IV THERAPY
Bandage for covering injection site when completed

If you suspect an anaerobic infection, obtain a special anaerobic culture vial.
Therapeutic
For therapeutic injections, you also need to obtain 1 bottle of
0.25% preservative-free bupivacaine (or equivalent) and 1
bottle of methylprednisolone acetate 40 mg/mL or equivalent.
Explain to the patient that the joint may be painful for up
to 24 hours after the injection.
The full benefit from a corticosteroid injection may take
several days.
The joint should also be rested for 1-2 days.
Preparation and Anesthesia

Confirm that you have all the required materials.
Stamp several labels with the patients name.
Complete the appropriate microbiology card.
Labels should be applied to all clinical specimens (or the
lab will not accept them).
Review the patients current CBC (platelets), aPTT, and INR
if available.
In the outpatient setting, coagulation studies typically are
not ordered before arthrocentesis.
Instead, the patient is asked if he or she is taking warfarin
or other blood thinners.
Make sure there is not an artificial joint.
Review relevant X-rays of the joint if available.
It may be useful to have a nurse or fellow resident in the
room to assist you.
Position the patient, and mark the insertion site (after careful review of the appropriate anatomic landmarks).
Confirm that the patient does not have a history of allergy to
lidocaine or iodine.
Also ask about drug allergies in general.
Place a disposable pad under the joint.
Open the kit on a bedside table.
Pour iodine into the iodine cup.
Change into sterile gloves.
877
Prepare the skin using gauze dipped into the iodine solution.
Remember to allow 5 minutes to dry or there is little bacteriocidal effect.
Drape the fenestrated drape over the insertion site.
Wipe the area with a sterile alcohol swab.
OptionalRaise a skin wheal with lidocaine by using a 25gauge 1-inch needle attached to a 6-cc syringe.
OptionalInfiltrate anesthetic into SQ tissue in the direction
that the arthrocentesis will occur, aspirating as you go, so
as not to inject anesthetic directly into a blood vessel.
Remove the anesthetic needle and syringe and place them
back on the tray.
Specific JointsShoulder, Elbow, Wrist, Knee, Ankle

Shoulder Joint
To aspirate the glenohumeral joint, use either a posterior or
anterior approach.
For the posterior approach, rotate the shoulder internally
across the chest, which opens the joint space.
Identify the sulcus between the head of the humerus and the
acromion.
Mark the insertion site with skin indentation 1 cm inferior and
1 cm medial to the lateral edge of the acromion process.
NoteAvoid going too far inferiorly with this approach
because you may enter the quadrangular space and risk hitting the axillary artery.
Prepare the joint, and anesthetize the insertion site as
described under Preparation and Anesthesia.
Connect the 18-gauge 1.5-inch needle to the 6-cc syringe.
A longer needle may be needed depending on body habitus; consider this for all the injections.
Advance the needle through the skin wheal, perpendicular to
the skin aiming for the coracoid process anteriorly.
Aspirate as much fluid as can be easily obtained.
TherapeuticIf a therapeutic injection is to be performed,
attach a 25-gauge 1.5-inch needle to another 6-mL syringe
and inject a mixture of 2 mL 0.25% preservative-free bupivacaine or equivalent and 1 mL 40 mg/mL of methylprednisolone acetate or equivalent.
The solution should go in smoothly if the needle is within the
joint space.
878
IV THERAPY
Remove the needles, and place a bandage over the site.
Elbow Joint
Flex the elbow to 90.
Have the patient rest the ulnar side of the hand on a table,
allowing the thumb to point upward.
Identify a triangle involving the lateral epicondyle of the
humerus, the olecranon process, and the head of the radius.
The radial head is identified by having the patient supinate
and pronate the forearm while you palpate for movement in
the area.
The needle will be directed in the space just inferior to the lateral epicondyle and superior to the olecranon process of the
ulna and proximal to the head of the radius.
Mark the site with a skin indentation.
Prepare the joint and anesthetize the insertion site as described
under Preparation and Anesthesia.
Connect a 20-gauge 1.5-inch needle to a 6-mL syringe.
Introduce the needle perpendicular to the surface of the
skin.
Advance the needle through the skin wheal.
attach a 25-gauge 1-inch needle to another 6-mL syringe
and inject a mixture of 1 mL 0.25% preservative-free bupivacaine or equivalent and 1 mL of 40 mg/mL methylprednisolone acetate or equivalent.
joint space.
Wrist Joint
Place a rolled towel under the wrist, which opens the joint
space.
The needle should be directed at a site on the dorsal wrist lateral to the extensor digitorum communis tendon, proximal to
the indentation of the capitate bone.
A concave space can be palpated here as the wrist is flexed
879
and extended; this space indicates the correct position for

needle placement.
Avoid the dorsal metacarpal vein, interns vein, when using
this approach.
Mark the site of insertion with a skin indentation.
Connect a 20-gauge 1.5-inch needle to the 6-mL syringe.
Advance the needle through the skin wheal, perpendicular to
the skin.
attach a 25-gauge 1-inch needle to another 6-mL syringe
and inject a mixture of 0.5-1 mL 0.25% preservative-free
bupivacaine or equivalent and 1 mL of 40 mg/mL of methylprednisolone acetate or equivalent.
joint space.
Knee Joint
Confirm the effusion.
Position the patient lying down on the bed, and slightly flex
the knee with a towel placed under the knee.
A lateral, medial, or inferior approach may be used. The
medial approach is discussed here.
The site of entry medially is just below the middle point for
the patella.
Introduce the needle parallel to the ground toward the intracondylar notch of the femur.
With this approach, there is no major artery nearby, but an
infrapatellar branch of the saphenous nerve is nearby.
Connect the 18-gauge 1.5-inch needle to a 6-mL syringe (a
35-mL syringe may be used if a large volume of fluid is
anticipated).
Advance the needle through the skin wheal, parallel to the
ground, proceeding under the patella at a 20-40 incline
from parallel.
880
IV THERAPY
You may hit the ostium of the undersurface of the patella.

This is painful for the patient. If this occurs, withdraw the
needle slightly, reposition, and aim more inferiorly.
You will often feel a pop or lessening of resistance as the
needle enters the joint space.
As the fluid is aspirated, it can be milked down by controlled pressure with one hand placed over the suprapatellar
pouch.
and inject a mixture of 3-4 mL 0.25% preservative-free
bupivacaine and 1 mL of 40 mg/mL of methylprednisolone.
joint space.
Remove the needles, hold pressure for 5 minutes (to reduce
any hematoma or ecchymosis), and place a bandage over
the site.
Ankle Joint
The ankle joint is composed of the tibiotalar joint, subtalar
joint, and talonavicular joint.
The tibiotalar joint is aspirated or injected.
The patient should be lying down, with the ankle in neutral
position.
Identify the tibialis anterior tendon and the extensor hallucis longus tendon by having the patient dorsiflex the
foot.
Identify the hollow medial or lateral to these two tendons at
the articulation of the tibia and the talus.
You should inject medially or laterally to these tendons to
avoid the dorsalis pedis artery.
Prepare the joint, and anesthetize the insertion site as
described under Preparation and Anesthesia.
Connect the 20-gauge 1.5-inch needle to the 6-mL syringe.
Direct the needle medially or laterally to the extensor hallucis
longus tendon and the anterior tibialis tendon.
881
Direct the needle tangentially to the curve of the talus and

slightly laterally.
It must be inserted approximately 3 cm before fluid will be
obtained.
Advance the needle through the skin wheal, aspirating as
you go.
and inject a mixture of 1-2 mL 0.25% preservative-free bupivacaine or equivalent and 1 mL of 40 mg/mL or equivalent
of methylprednisolone.
joint space.
Synovial Fluid Analysis

Features of synovial fluid characteristic of various conditions are listed in Table 1.
LUMBAR PUNCTURE
Indications
For internists, lumbar puncture is performed primarily for
the diagnosis of
Central nervous system infection (meningitis, encephalitis, neurosyphilis)
If suspicion is high, begin antibiotics or antivirals before
procedure.
Demyelinating conditions (Guillain-Barr syndrome, multiple sclerosis)
Other (pseudotumor cerebri, malignancy)
Contraindications
Local lumbar skin infection over puncture area
Suspicion of empyema
Increased intracranial pressure from a mass lesion
Uncooperative or combative patients (relative contraindication)
Severe bleeding diathesis (relative contraindication)
Platelet count <50 109/L (relative contraindication)
882
Table 1. Synovial Fluid Analysis

Condition
Normal
Noninflammatory (e.g.,
DJD)
Acute gout
% PMNs
Glucose %
serum level
Crystals under
polarized light
Appearance
WBCs/L
Clear
Clear
<200
<2,000
<25
<25
95-100
95-100
None
None
Turbid
2,000-5,000
>75
80-100
~75
Negative birefringence,
needle-like crystals
None
Turbid
2,000-10,000
50-75
Turbid
5,000-50,000
>75
Septic arthritis
Purulent/turbid
>50,000*
>75
80-100
<50
Positive birefringence,
rhomboid crystals
None
DJD, degenerative joint disease.

*Higher with untreated or virulent organisms.
Data from www.uptodate.com [cited 2005 May 2] and Cush JJ, Lipsky PE. Disorders of the joints. In: Fauci AS, Martin JB, Braunwald E,
Kasper DL, Isselbacher KJ, Hauser SL et al, editors. Harrisons principles of internal medicine. Vol 2. 14th ed. New York: McGraw-Hill;
1998. p. 1931.
883
IV THERAPY
Inflammatory (e.g.,
rheumatoid arthritis)
Pseudogout
Equipment
Kits are available that contain the following:
Skin needle (25 gauge with 3-mL syringe)
Infiltration needle (22-gauge 1.5-inch needle)
Spinal needle with stylet
Lidocaine HCl, 1%
Sterile gloves
Three-way stopcock
Manometer
Extension tube, 5 inches
Prelabeled specimen vials with caps, 10 mL
Gauze pads
Sterilization swab sticks
Fenestrated drape
Bandage
Procedure
Perform an ophthalmoscopic exam to assess for papilledema
or retinal hemorrhage.
Perform CT of the head, check platelets and aPTT, PT, and
INR as indicated.
Position the patient in the lateral decubitus or sitting position.
Proper positioning with frequent assessment will ensure
successful and safe placement of the lumbar needle.
Have the patient flex the spine anteriorly with his or her chin
on the chest.
Ensure that the patient keeps the shoulders and hips perpendicular to the bed.
Arch the patients back to open the vertebral spaces to allow
easier entrance of the spinal needle into the subarachnoid space.
Identify the L3-4 interspace at the level of the iliac crests.
Mark the space over the midline with a skin indentation.
Prepare the skin over the preselected interspace, as well as
one above and below, with antiseptic solution.
Prepare equipment on an adjacent table using sterile technique.
Verify that all the necessary items are present and working
properly.
Assemble the manometer and attach the three-way stopcock.
Align the specimen tubes in order in an upright position on
the tray.
884
IV THERAPY
Drape the area with sterile draping, and remove excess iodine
from the marked insertion site.
Use a skin wheal to anesthetize the skin.
With the infiltration needle, anesthetize deeper into the posterior spinous region after superficial analgesia is adequate.
Select the spinal needle with stylet in place, and verify that
superficial anesthesia is still adequate.
Instruct the patient that he or she may feel pressure.
If sharp pain is felt, the anesthesia is not adequate.
Also, the patient should inform the operator if he or she feels
pain down either leg at any time during the procedure.
With the bevel up, direct the needle in the midsagittal plane
cephalad toward the umbilicus.
If immediate resistance is felt, the needle should be withdrawn slightly and redirected.
The subarachnoid space is often deeper than expected,
and you may feel a pop upon penetrating the ligamentum flavum and dura mater.
Check for CSF return frequently by withdrawing the stylet
to look for fluid return.
After CSF has been obtained, measure the opening pressure
with the three-way stopcock and manometer.
After asking the patient to straighten his or her legs, measure the CSF meniscus in the manometer tube.
Empty the fluid from the manometer into the first tube and
fill each subsequent tube with approximately 2-3 mL.
Reinsert the stylet, alert the patient that you are about to
remove the needle, and withdraw the needle.
Place the bandage over the insertion site.
Perform blood tests if needed (i.e., glucose).
Complications
Headaches occur in up to 30% of patients.
This complication can be minimized by using a 20-gauge
or smaller needle and by reinserting the stylet before withdrawing the needle.
Nerve root herniationavoid by retracting the needle with
a well-fitting stylet in place
885
Transient cranial nerve VI palsycaused by traction on the

cranial nerve from removal of large amounts of CSF
CSF Analysis
CSF features associated with various conditions are listed
in Table 2.
PARACENTESIS
Indications
Evaluation of new ascites
Evaluation of established ascites for infection
Relief of respiratory compromise
Relief of gastrointestinal complaints
Impending peritoneal rupture
Contraindications
Uncooperative or agitated patient
Pregnancy
Bowel obstruction
Suspected adhesion of bowel to abdominal wall
Adjacent infection
Abdominal wall cellulitis
Infraumbilical surgical scar (excludes a midline approach)
Hematoma
Equipment
A catheter device such as an 8F catheter over 18-gauge
introducer needle with stopcock
Lidocaine
Povidone-iodine swab sticks
Needles (25 and 22 gauge)
Two syringes
Scalpel blade with handle
Evacuated fluid collection bottles
Drainage tubes with and without needles
Specimen vials
Sterile gloves
Bandage
IV albumin if the projected volume removed will exceed
4 L of ascitic fluid
886
Table 2. CSF Findings in Various Conditions

Pressure,
mm H2O
Cell count, mm3,

& differential
Normal
100-180
Bacterial meningitis
200-300
0-5 WBC (no PMNs)

Traumatic tap may have
1 WBC per 700 RBCs
>100 WBCs (mostly
PMNs)
100-300 monocytes
Condition
90-200
Herpes encephalitis
90-400
>200
PCR, polymerase chain reaction.
50-500 lymphocytes
(RBCs present in 80%,
PMNs may be present
early)
>1,000 RBCs
Protein, mg/dL
50-175 (alternative =
CSF/blood ratio
of 0.67)
<40
15-45
Normal (decreases
slightly with mumps)
Normal (small % of
patients <40 years)
50-100
Normal
100-1,000 (rapid antigen test)
50-100 (PCR for antigen)
>45 (for each 1,000 RBCs,

protein increases by 1 mg/dL)
887
IV THERAPY
Viral meningitis
Glucose, mg/dL
One recommendation is to give 25 g of albumin for

more than 4 L removed.
Procedure
Have the patient lie in the horizontal dorsal decubitus position.
Raise the bed to a comfortable level for the operator.
Reexamine for location of the ascitic fluid, and mark an
insertion site with an indentation.
A midline insertion should be placed 2 cm inferior to the
umbilicus. A lateral approach is placed 5 cm cephalad and
medial to the anterior superior iliac crest, typically on the
left side (to avoid the cecum).
Prepare the skin with the povidone-iodine solution.
Prepare equipment on an adjacent table using sterile technique.
Examine the kit to verify that all the necessary items are
present and working properly.
Remove excess iodine from the marked insertion site.
Drape the area with sterile draping.
After superficial analgesia is adequate, infiltrate deeper
to anesthetize to the peritoneum.
Use a small scalpel to make a small superficial incision at the
marked site (~3 mm long).
Take care not to puncture the peritoneum in patients with
abdominal wall atrophy.
Insert the catheter device into the incision site approximately
perpendicular to the abdominal wall.
Create a Z tract to reduce subsequent oozing in two different
ways:
Use the free hand to stretch the skin near the entry site
until the catheter is inserted and fluid is obtained.
Make a Z tract by using a zigzagging approach on entry by
varying the catheter angle on insertion to produce a selfsealing site.
While using a twisting motion with the catheter, draw back
slowly on the syringe until ascitic fluid is visualized.
Once ascitic fluid is visualized, remove the introduced needle
while advancing the catheter into the peritoneal cavity.
Attach the plastic tubing to the catheter via the three-way
stopcock, and verify catheter placement by withdrawing
888
IV THERAPY
ascitic fluid into a large syringe.

If the procedure is for diagnostic purposes only, this fluid
can be sent for the desired testing.
If the procedure is performed for therapeutic benefit, attach
one end of plastic tubing to the stopcock and the other end
to a needle.
Place the needle in the evacuated container.
On opening the stopcock to the tubing, ascitic fluid return
should be seen immediately.
If the flow of fluid is inadequate or stops during the procedure, the catheter can be repositioned gently with a twisting motion or slightly withdrawn until fluid flow improves.
When desired amounts of fluids are obtained or flow of fluid
stops despite catheter repositioning, withdraw the catheter.
Dress the site with a bandage.
After paracentesis is completed and the patient stabilized,
any necessary blood tests can be performed (e.g., albumin).
Complications
Common complicationlocal hematoma
Bowel entry
Hemoperitoneum
Infection
Ascites leak
Testing
Fluid testing usually includes
CBC and differential
Gram stain and bacterial cultures
Albumin
SAAG = [serum albumin (SA)] [ascites albumin (AG)]
(Table 3)
Total protein
Additional testing may include
Amylase
Glucose
LDH
Bilirubin
889
Triglycerides
Cytology
Acid-fast bacilli and mycobacterial cultures
Indicate to store remaining fluid
Abnormal test values and their clinical importance are listed
in Table 4.
THORACENTESIS
Indications
Diagnostic evaluation of pleural effusions of unknown etiology
Therapeutic indication for symptomatic pleural effusions
Contraindications
Uncooperative or agitated patient
Small loculated effusions (diagnosed by chest X-ray)
Insufficient amount of pleural fluid (<10 mm on lateral decubitus film)
Bleeding diathesis or excess anticoagulation (platelets
<25 109/L)
Marginal respiratory reserve or unstable medical condition
Positive end-expiratory pressure
Adjacent infection (cellulitis) that may be introduced into
the pleural space
Equipment
Table 3. Ascitic Fluid Analysis

SAAG, g/dL
Serum total protein, g/dL
1.1
890
<2.5
>2.5
Cirrhosis
Portal
hypertension
Congestive
heart failure
Pulmonary
hypertension
Right-sided
heart failure
Budd-Chiari
syndrome
<1.1
Malnutrition
Nephrotic syndrome
Peritoneal
carcinomatosis
TB
IV THERAPY
Table 4. Abnormal Values and Clinical Importance of
Additional Tests
Additional test
Abnormal value
Amylase
>100 g/dL
Triglycerides
PMNs
Glucose
>200 mg/dL
>250 cells/mm3
<50 mg/dL
Bilirubin
>6 mg/dL
Clinical importance
Pancreatic source, intestinal
rupture
Ruptured lymphatic system
Bacterial peritonitis
Spontaneous bacterial
peritonitis or gut perforation
Gallbladder or upper gut
perforation
A catheter device such as an 8F catheter over an 18-gauge

introducer needle with stopcock
Lidocaine
Povidone-iodine swab sticks
Needles (25 and 22 gauge)
Two syringes (large and small)
Scalpel blade with handle
Evacuated fluid collection bottles
Drainage tubes with and without a needle
Specimen vials
Sterile gloves
Arterial blood gas (ABG) (heparinized) syringe in a bag
of ice (for pH analysis)
Mask
Bandage
Procedure
Check platelets aPTT, PT, INR as indicated, and view the
chest X-ray to verify the side of the effusion.
Verify the side of the effusion again.
Bringing the film into the room with you will help you
avoid tapping the wrong side.
Have the patient sit comfortably on the edge of a chair or
bed with arms crossed in front.
891
Select the insertion site for fluid removal ~1 to 2 interspaces

below the fluid level and in line with the posterior scapular line.
Do not go below the 10th intercostal interspace.
Mark the insertion site with a skin indentation.
Prepare the equipment on an adjacent table using sterile
technique.
Prepare the skin with povidone-iodine solution.
Examine the kit to verify that all the necessary items are
present and working properly.
Remove excess povidone-iodine from the marked insertion
site, and drape the area with sterile draping.
Use the 22-gauge needle to infiltrate the anesthetic into the
rib and pleura.
Continue to aspirate and inject as you advance by guiding the
needle over the superior margin of the rib until the parietal
pleura is entered.
Use the scalpel to make a small horizontal incision over the rib.
Insert the catheter device in the same tract as the anesthesia
needle, drawing slowly on the syringe until pleural fluid is seen.
Once pleural fluid is seen, slowly remove the needle while
advancing the catheter.
Verify catheter placement by withdrawing pleural fluid
into a large syringe.
If the procedure is for diagnostic purposes only, this fluid
can be sent for the desired testing.
If the procedure is performed for therapeutic benefit, attach
one end of plastic tubing to the stopcock and the other end
to a needle.
Place the needle in the evacuated container.
On opening the stopcock to the tubing, pleural fluid return
should be seen immediately.
If the flow of fluid is inadequate or stops during the procedure, the catheter can be repositioned gently with a
twisting motion or slightly withdrawn until fluid flow
improves.
Do not replace the needle!
Once the desired amount of fluid is obtained or fluid flow
stops despite catheter repositioning, withdraw the catheter.
Dress the site with a bandage.
892
IV THERAPY
After thoracentesis has been completed and the patient stabilized, the necessary blood tests can be performed (i.e.,
serum protein and LDH).
Obtain a chest X-ray to assess for pneumothorax, and
personally view the film.
Complications
Pain in up to 20% of patients
Pneumothorax in up to 10% of patients
Dry tap
Bleeding
Empyema
Visceral trauma (spleen, heart, liver)
Reexpansion pulmonary edema
Testing
Fluid testing may include
Gram stain and bacterial cultures
LDH
Protein
Cytology
pH using a heparinized ABG syringe that is kept on ice
Amylase
Glucose
Triglycerides
Acid-fast bacilli and fungal evaluations
Anaerobic culture
Transudate and exudate fluids are compared in Table 5.
Additional features of exudate are listed in Table 6.
Pleural fluid tests and their clinical importance are listed in
Table 7.
893
Table 5. Comparison of Transudate and Exudate Fluid

Analysis
Fluid
Feature
Appearance
Protein ratio (pleural/serum)*
LDH ratio (pleural/serum)*
Total LDH*
Transudate
Exudate
Straw-colored
<0.5
<0.6
Turbid
>0.5
>0.6
>200
*Meeting 1 of the above criteria has a sensitivity of 70%, 2 criteria have 97%,
and 3 have a 99% sensitivity (Light criteria [Light RW, MacGregor I,

Luchsinger PC, Ball WC Jr. Pleural effusions: the diagnostic separation of
transudates and exudates. Ann Intern Med. 1972;77:507-13]).
Table 6. Additional Features of Exudates

Feature
Value
Pleural fluid protein*

Pleural fluid cholesterol*
Pleural fluid LDH*
>2.9 g/dL
>45 mg/dL
>45% of normal serum value
*In one study, the use of the values in this table was as successful in differentiating transduate from exudate as the use of 2 or 3 of the Light criteria in
Table 5.
Table 7. Pleural Fluid Tests

Test
Glucose <60 mg/dL
pH
Clinical importance
Suggests rheumatoid pleurisy, empyema,
malignancy, TB
<7.3 indicates an increased need for
pleural space drainage in parapneumonic
effusions
Acute pancreatitis, esophageal rupture,
malignancy
Amylase (> normal

serum amylase or
ratio >1.0)
Total pleural fluid LDH >1,000 suggests empyema, rheumatoid
arthritis
Triglycerides >115
Chylothorax
mg/dL
894
IV THERAPY
RENAL REPLACEMENT THERAPIES
Steven J. Younger, M.D.
John W. Graves, M.D.
INDICATIONS FOR DIALYSIS (AEIOU)

Remember
A is for refractory acidosis, i.e., pH is <7.0 and not improving.
E is for refractory electrolyte disturbance, i.e., potassium is
>6.0 with or without ECG changes despite medical
management.
I is for intoxicants, i.e., overdose of dialyzable substances
(Table 1).
O is for refractory fluid overload (failure to respond to escalating doses of diuretics).
U is for uremia, i.e., pericarditis, neuropathy, or decline in
mental status not otherwise explained.
DEFINITIONS
Dialysis
A transport process by which a solute diffuses through a
concentration gradient from one compartment to another
Typically, hemodialysis maintains water but
Removes potassium, creatinine, and BUN
Replaces bicarbonate and calcium
Filtration
The process by which water and middle-sized molecules
(>5,000 daltons) move across a membrane, not because of a
concentration gradient but by hydrostatic pressure and a
mechanism called solvent drag
This process removes solutes such as potassium and urea in
the same concentration as plasma.
Special abbreviations used in this chapter: AV, arteriovenous; VV, venovenus.

895
Table 1. Common Agents for Which Hemodialysis Enhances

Elimination
Barbiturates
Bromides
Chloralhydrate
Alcohols
Ethanol
Isopropanol
Acetone
Methanol
Ethylene glycol
Lithium
Procainamide
Theophylline
Salicylates
Heavy metals (possible)
Trichloroethanol
Atenolol
Sotalol
Substitution fluid with lower concentrations of electrolytes

is often needed to prevent hypovolemia while reducing plasma concentrations of solutes.
Diafiltration
Combination of dialysis and filtration
Arteriovenous (AV)
A single-lumen catheter uses the blood pressure gradient to
deliver arterial blood into the extracorporeal circuit returning the treated blood to the venous system.
Venovenous (VV)
The use of a double-lumen catheter (more common) or two
different catheters placed within the venous system that
requires an external pump to push the blood into the extracorporeal circuit
INTERMITTENT RENAL REPLACEMENT THERAPIES

Hemodialysis
Standard modality for hemodynamically stable patients
896
IV THERAPY
Advantage
Most effective means of renal replacement therapy
Disadvantages
Inconvenience
Difficulty with vascular access (thrombosis and infections)
Severe dietary and fluid restrictions
Acute hemodialysis
Performed through a temporarily placed dual-lumen
catheter (e.g., Mahukar or Quinton) either in a femoral or
jugular vein
Subclavian access is not recommended because of possible subclavian stenosis interfering with fistula placement
in that arm.
Chronic hemodialysis
Performed through
Brescio-Cimino AV fistulaeither a connection
between the radial or brachial vascular systems; best
long-term access
Gore-Tex synthetic graftthe best alternative if BrescioCimino AV fistula is not technically possible
Disadvantage, a foreign body and more likely to be
infected
Tunneled cathetercan also be used for long-term
access but has the most potential for infection
Initiating hemodialysis
Patients in acute renal failure new to dialysis should have
runs of 1-2 hours for 2 consecutive days.
This is to avoid disequilibrium syndromeAggressive
dialysis markedly decreases plasma concentration of urea.
Because intracellular urea cannot move out into the plasma quickly enough, there is disequilibrium between the
intracellular and extracellular urea concentrations. This
syndrome may cause mild (headache, cramping, nausea)
to severe (seizures, cerebral herniation, and death)
symptoms.
After patients are stabilized and chronic dialysis is
needed, the runs are typically for 4-6 hours 3 days a
week.
897
Peritoneal Dialysis
Advantages
Patient controls own treatment.
May be done at home
Less severe fluid and dietary restrictions than for hemodialysis
Diabetic patients can place insulin into dialysate to avoid
SQ injections.
Disadvantages
Weight must be <80 kg (otherwise must do more than 5
exchanges/day)
Mental and physical dexterity required to change the
dialysate fluid regularly.
Risk of peritonitis is the major disadvantage (scarring,
pain, and sepsis).
Peritoneal dialysis uses the patients abdominal lining as the
semipermeable membrane (the surface area of the abdominal lining is 1 m2, which is almost the same as the surface area
of the renal glomeruli).
Fluid (dialysate) is placed in the abdomen through a plastic catheter.
The fluid is allowed to sit (dwell) in the abdomen for 30
minutes to 4 hours.
BUN, potassium, and other molecules diffuse through the
peritoneal lining and accumulate in the fluid.
Water is pulled into the peritoneal dialysate by having a
very high glucose concentration (1.5%-4.25%), which
makes glucose osmotically active and draws water from the
plasma into the dialysate.
The fluid is then drained from the peritoneal cavity and the
cycle repeated with fresh dialysate.
CONTINUOUS RENAL REPLACEMENT THERAPIES
These are used only in acute renal failure for those who are
not hemodynamically stable.
In choosing which form of continuous therapy to use, consider the following:
Goals of therapy
Which forms of therapy are available
Which forms of continuous therapy the nephrologist and
staff are comfortable with using
898
IV THERAPY
For several reasons, intermittent acute hemodialysis causes

more hemodynamic problems than the continuous therapies:
Excess plasma volume is removed and can decrease blood
pressure.
Dialysis can cause major shifts of solutes, whereas hemofiltration removes solute at the same concentration as in the
plasma. The shifts of solute out of the plasma mean that
the intracellular osmolality is higher than in plasma and
water then shifts out of the vascular space into the intracellular space.
Dialysis membranes used in intermittent hemodialysis are
not as porous as the membranes used in hemofiltration
and the middle- to large-sized molecules are thought to
have more vasodilatory or cardiodepressant effects.
Continuous AV hemofiltration
This modality of renal replacement is best for hemodynamically unstable patients in whom refractory fluid overload is the major problem (filtration does remove very
small amounts of solutes as well).
DisadvantageArterial access is needed.
Continuous VV hemofiltration
Similar to continuous AV hemofiltration except arterial
access is not needed.
Best for fluid removal
Continuous AV hemodialysis
Uses a dialysate to run countercurrently, but set to remove
fluid at a low rate
Use if solute removal is more important than fluid balance and patient is hypotensive
Continuous VV hemodialysis
Very similar to continuous AV hemodialysis but different
access
Continuous AV hemodiafiltration
Similar to continuous AV hemodialysis except the ultrafiltration rate is allowed to be higher than needed to establish euvolemia and replacement fluid is then placed back
into the plasma
Use for hemodynamically unstable patients who need
899
large amounts of solute removed and who have arterial

access
Continuous VV hemodiafiltration
Same as continuous AV hemodiafiltration except arterial
stick is not needed
RENAL TRANSPLANTATION
The treatment of choice for chronic renal failure
Advantagesbetter quality of life and decreased mortality
compared with chronic hemodialysis and peritoneal dialysis
methods
Contraindications
HIV or other active infection
Malignancy with expected short life span
Poorly controlled psychosis
Active substance abuse
Any illness likely to end life within a year
DisadvantagesAvailability of organs is the usual disadvantage to transplantation, but with increasing use of living
related and unrelated donors (some centers are even trying
cross-match positive kidneys), renal transplantation should
be considered for nearly all patients with chronic renal failure.
900
IV THERAPY
STEROID THERAPY
Stanley I. Martin, M.D.
William F. Young, Jr., M.D.
INDICATIONS
The indications for steroid therapy by medical specialty are
listed in Table 1.
CLASSIFICATION
Potency and duration of action of steroids are listed in Table 2.
MONITORING
Monitoring response to steroids varies widely and depends
on the disease being treated.
Side effects of steroids that should be monitored universally
include
Bone mineral densitymeasured annually
Intraocular pressurechecked at least every 6 months
Blood glucosemonthly for outpatients, daily for
inpatients
Blood pressuremonthly for outpatients, daily for
inpatients
Consider Pneumocystis carinii prophylaxis if long-term therapy.
Consider gastrointestinal tract protection with a proton pump
blocker, especially if patient is concurrently taking an NSAID.
PRESCRIBING
Oral steroids are absorbed almost 100% within about 30
minutes.
Topical steroid absorption depends on the area of the body
to which agent is applied, e.g., intertriginous folds have a
higher rate of absorption than the forearm.
Salicylic acid and occlusive dressings enhance cutaneous
absorption.
Alternate-day dosing was devised to alleviate undesirable
901
side effects of long-term high-dose therapy with less suppression of hypothalamic-pituitary-adrenal axis.
Begin use within 3 weeks after starting treatment.
Prescribe approximately twice the usual daily dose of
steroids every other day and use a shorter-acting agent.
COMPLICATIONS
Withdrawal
The most frequent complication from steroid withdrawal is
flare-up of underlying disease for which the patient was
being treated.
Withdrawal can also lead to adrenocortical insufficiency
from suppression of hypothalamic-pituitary-adrenal axis.
Symptoms may include myalgias, fever, hypotension, nausea and vomiting, and confusion.
Pseudotumor cerebri is a rare effect of acute withdrawal.
Supraphysiologic Doses
Side effects at supraphysiologic doses are listed in Table 3.
902
IV THERAPY
Table 1. Indications for Steroid Therapy by Medical
Specialty
Medical specialty
Allergy & immunology
Dermatology
Endocrinology
Indications
Allergic rhinitis
Triamcinolone & fluticasone are
used 2 sprays/nostril daily
Flunisolide, budesonide, &
beclomethasone are used 2 sprays/
nostril twice daily
Beclomethasone also comes in 84 g
preparation which is applied 4
sprays/nostril daily
Inflammatory disorders of skin
1% Hydrocortisone cream topically
twice daily
Oral glucocorticoids such as 40-120
mg of prednisone daily are used for
severe disease (e.g., Stevens-Johnson
syndrome) or exacerbations of
chronic disorders
Exogenous glucocorticoid replacement
Hydrocortisone 15 mg each AM &
5-10 mg each PM (first choice) or
prednisone 3-7.5 mg daily or
dexamethasone 0.25 mg daily
closely mimic the bodys normal
supply
Mineralocorticoids are needed only
in primary adrenal insufficiency
Stress dosing
In mild illnesses, double or triple
steroid dose
For severe trauma or surgical stress,
hydrocortisone 50 mg IV every 6
hours or 100 mg IV every 8 hours
is recommended
903
Table 1 (continued)
Medical specialty
Gastroenterology
Hematology &
oncology
Nephrology
904
Indications
Ulcerative colitis or Crohn disease
acute exacerbations
Prednisone 10-120 mg PO daily
depending on severity
80% of patients have biopsy-proven
remission with prednisone 40-60 mg
daily until transaminases decrease,
then taper to 7.5-10 mg as tolerated
Autoimmune hemolytic anemia
(Coombs-positive)
Prednisone 1 mg/kg daily can be
tried; higher doses in severe
hemolysis; may require small
maintenance doses for long periods
ITP
Prednisone 1-1.5 mg/kg daily is
usual treatment; refractory disease
may respond to pulsed, higher-dose
glucocorticoids
Chemotherapy
Used in combination with various
agents in leukemias, lymphomas,
multiple myeloma, amyloidosis, etc.
Minimal change glomerulonephritis
Start prednisone 1-2 mg/kg for 6
weeks, then taper over 6-8 weeks;
90% will have remission in 3 months
Membranous & membranoproliferative
glomerulonephritis with focal sclerosis
Conflicting data on efficacy of steroid
therapy; many nephrologists recommend 120 mg prednisone qod for
8-10 weeks, with a 1-2 month
taper; response must be monitored
Rapidly progressive glomerulonephritis
(lupus nephritis WHO type III and IV)
IV steroid pulse 1 g daily 3 days
IV THERAPY
Table 1 (continued)
Medical specialty
Neurology
Indications
Spinal cord injuries within 8 hours
Methylprednisolone up to 30 mg/kg
initially, followed by 5.4 mg/kg every
hour for 23 hours causes pronounced
decrease in neurologic deficits
Primary or metastatic CNS neoplasms
with intracranial hypertension or
cord compression
Dexamethasone 4-6 mg PO or IV
every 6 hours (controlled clinical
trials do not support steroid use for
traumatic injuries of the brain or for
stroke)
Multiple sclerosis
Relapses can be treated with steroids;
efficacy is controversial; methylprednisolone for 5 days can be used;
no consensus about optimal dosages
or duration of therapy
Myasthenia gravis
Prednisone 60-100 mg PO daily until
improvement is sustained for about
2 weeks, then gradually taper to
5-15 mg PO daily over several
months
Dexamethasone high-dose administration has been highly successful
when used in a 10-day course &
then repeated (e.g., 20 mg PO daily)
Also, low-dose alternate-day therapy
with prednisone 25 mg PO daily &
then increasing by 12.5 mg PO qod
until 100 mg PO qod is achieved.
This should be done for at least 3
months because improvement may
not occur for up to 7 weeks. Taper
doses as allowed
CNS vasculitides
Methylprednisolone pulse 1 g IV for
3 days
905
Table 1 (continued)
Medical specialty
Ophthalmology
Pulmonology
906
Indications
Inflammation of the outer eye &
anterior segment
Topicals, such as 0.1% dexamethasone
sodium phosphate solution applied
2 drops to the conjunctiva every
4 hours while awake, can be
beneficial in noninfectious conjunctivitis. Do not use for bacterial,
viral, or fungal conjunctivitis
Inflammation of the posterior segment
Systemic steroids
Severe asthma or COPD exacerbations
Methylprednisolone 60-125 mg
every 6-12 hours
As the attack resolves, switch to
prednisone 40-60 mg PO daily;
attempt to taper over 5-14 days, then
stop altogether
For less severe exacerbations of
asthma, prednisone 40-60 mg daily
for 5-7 days
Results of studies have not shown any
benefit in treatment, at least in early
stages of disease. Steroids are
commonly used at high doses,
usually with IV methylprednisolone,
similar to acute asthma or COPD
exacerbations
Pneumocystis carinii pneumonia
If PaO2 <70 or A-a gradient >35,
prednisone 40-60 mg PO bid for 5
days, 20 mg bid on days 6-10, &
20 mg daily on days 11-21
IV THERAPY
Table 1 (continued)
Medical specialty
Rheumatology
Transplantation
Indications
SLE, sarcoidosis, rheumatoid arthritis,
& vasculitides such as polyarteritis
nodosa, Wegener granulomatosis,
temporal arteritis
Specific doses depend on disease,
organ involvement, severity, & other
factors
Gout
Prednisone 40-60 mg PO daily for
patients with contraindications to
NSAIDs (e.g., renal failure)
Tendinitis, bursitis, & arthritis
Intra-articular injections for inflammatory, crystal, and osteoarthritis.
Dose depends on joint size. Use
5-20 mg of triamcinolone acetonide
or equivalent. Give injections
sparingly with at least 3 months
between each dose
At time of operation
Prednisone 50-100 mg usually given
in conjunction with other immunosuppressive agents; the patients
doses are tapered to lower maintenance regimen as effects of organ
rejection are monitored
A-a, alveolar-arterial; bid, twice daily; CNS, central nervous system; ITP,
idiopathic thrombocytopenic purpura; qod, every other day; SLE, systemic

lupus erythematosus.
907
908
Table 2. Glucocorticoid Preparations

Potency
Cortisol
Cortisone
Fludrocortisone
Prednisone
Prednisolone
Methylprednisolone
Triamcinolone
Betamethasone
Dexamethasone
NA, not applicable.
1
0.8
10
4
4
5
5
25
25
Duration of activity
Short
Short
Short
Intermediate
Intermediate
Intermediate
Intermediate
Long
Long
Equivalent doses, mg
Aldosterone activity
20
25
NA
5
5
4
4
0.75
0.75
1
0.8
125
0.8
0.8
0.5
0
0
0
IV THERAPY
Table 3. Side Effects at Supraphysiologic Doses
Cardiovascular
Hypertension
Atherosclerosis
Coronary artery disease
Dermatologic
Hirsutism, skin atrophy, striae, and purpura
Endocrine
Hyperglycemia4 increase in risk of diabetes mellitus with
long-term use
Truncal obesity
Hyperlipidemia
Growth suppression in pediatric patients
Sodium & fluid retention
Hypokalemia
Gastrointestinal tract
No peptic ulcer disease (unless concurrent use of NSAIDs or
alcohol)
Acute pancreatitisrare
Steroids can mask symptoms of life-threatening gastrointestinal
tract perforation & peritonitis, particularly worrisome in
patients with inflammatory bowel disease
Hematologic
Acutely, steroids lead to leukocytosis with neutrophilia &
lymphopenia, but usually with no left shift
Eosinophils & basophils tend to be suppressed
Infectious
Increased risk for infections with >10 mg of prednisone or
equivalent daily
PCP may develop in patients taking steroids equivalent to 30 mg
of prednisone daily for >2 months; in such cases, some
recommend TMP-SMX prophylactically
Beware of using steroids in vasculitides in which underlying
infection may have a role such as polyarteritis nodosa with
hepatitis B infection, steroids may exacerbate the infection
Musculoskeletal
Myopathy occurs in up to half of patients with long-term steroid
therapy; muscle enzymes are usually normal, but urine
creatinine level is often increased
909
Table 3 (continued)
Musculoskeletal (continued)
Osteoporosisrapid loss of bone density in first 6 months of
therapy, then at slower pace; a net reduction in calcium
absorption and enhanced urinary excretion stimulates
increased parathyroid hormone levels; trabecular bone (femoral
neck, distal radius, vertebral bodies) affected more than
cortical bone
Avascular necrosisincreased risk with SLE, renal transplantation, antiphospholipid syndrome, trauma, & alcoholism
(femoral head most at risk, distal femur, talus, humeral head,
proximal tibia, navicular, and scaphoid bones)
Ophthalmic
Posterior subcapsular cataracts
Glaucomatopical applications of ocular steroids can lead to
increased intraocular pressure; monitor if topical steroids are
used >2 weeks
Psychiatric
Acutelysteroids may cause minor confusion to severe
psychosis
Long-termanxiety & depression are common, as are
irritability, insomnia, & decreased libido
PCP, Pneumocystis carinii pneumonia; SLE, systemic lupus erythematosus.
910
IV THERAPY
TRANSFUSION THERAPY
Grace K. Dy, M.D.
Dennis A. Gastineau, M.D.
INDICATIONS
Indications for transfusion of cellular components are listed
in Table 1 at end of chapter.
Indications for transfusion of plasma derivatives are listed in
Table 2 at end of chapter.
Indications for special coagulation factor products are listed
in Table 3 at end of chapter.
SPECIAL MONITORING PARAMETERS
Platelet transfusion
When the next AM count is no higher than pretransfusion
level, measure 1-hour posttransfusion count.
If no or insignificant increase, consider platelet refractoriness from alloimmunization, sepsis, effect of antibiotics, or hypersplenism.
Frozen lymphocyte antibody panel to look for HLA alloimmunization
COMPLICATIONS OF TRANSFUSION THERAPY

Febrile nonhemolytic reaction
Increase in temperature of 1C without hemolysis
Alloantibodies in recipient against donor leukocyte or
platelet antigens
Usually seen in multiply transfused patients
Cannot distinguish from hemolytic reaction clinically,
evaluation for transfusion reaction required
Hemolytic transfusion reaction
Minor symptomsfever, chills, back pain
Major symptoms or signsdyspnea, chest pain, hemoglobinuria, oliguria, shock, intravascular coagulation and
911
fibrinolysis (formerly called disseminated intravascular

coagulation)
Stop transfusion, hydration, alkalization of urine.
InvestigateCheck for clerical error, repeat ABO/Rh typing, antibody screen on pre- and posttransfusion samples.
Anaphylactoid reaction
Nausea, abdominal cramping, diarrhea
Use washed product.
Allergic reactions
Urticaria
Circulating antibody against foreign donor serum
proteins
Treat with antihistamines.
Blood may be restarted if urticaria is sole reaction and
episode has resolved.
Transmission of microorganisms
Bacterial contaminationsymptoms similar to those of
hemolytic reaction, highest risk with platelet concentrates
Use of leukocyte-reduced products reduces but does not
eradicate risk of transmission of viral infection.
Volume overload
Bacterial contaminationsymptoms similar to those of
hemolytic reaction, highest risk with platelet concentrates
Use of leukocyte-reduced products reduces but does not
eradicate risk of transmission of viral infection.
Volume overload
Dyspnea, exacerbation of congestive heart failure, cardiogenic pulmonary edema
Use lowest rate of administration allowable in nonurgent
situations (1-2 mL/kg per hour in high-risk patients).
Use factor-specific concentrates.
Diuresis morphine (for severe pulmonary edema)
Hypotension
Patients taking angiotensin-converting enzyme inhibitors
receiving leukocyte-reduced products through bedside
filters
Use prestorage leukocyte-reduced products (bradykinin
is degraded in minutes).
Hypocalcemia, hyperkalemia
Seen in massive transfusion, defined loosely as >10 units
of whole blood or equivalent to one blood volume
912
IV THERAPY
Hemostasis and coagulation defects

Coagulopathy, dilutional thrombocytopenia during massive transfusions
Posttransfusion purpura 5-10 days after transfusion of
RBCs containing fragments of PlA1 platelet antigen
Frequently associated with severe bleedingtreat with
IV immunoglobulin; plasma exchange for nonresponse
to IV immnoglobulin
Seen mostly in multiparous women, previously transfused patients
Drug-induced thrombosis with desmopressin (DDAVP)
in patients with atherosclerotic vascular disease
Prolonged factor IX or XI concentrate infusion may be
associated with thromboembolic events (deep venous
thrombosis, pulmonary embolism, intravascular coagulation and fibrinolysis, rarely myocardial infarction).
Iron overloadtransfusion hemosiderosis
Seen in persons who received 60-200 units of RBCs
Prophylactic iron chelation (deferoxamine) in patients
with thalassemia
Immunological
Alloimmunization
Causes refractoriness to random-donor platelet products
Use leukocyte-reduced products when multiple transfusions are anticipated with ongoing therapy (e.g., acute
myelogenous leukemia).
Use cross-match negative single-donor apheresis product or HLA-matched product if alloimmunized.
Transfusion-associated lung injury
Rare; most often associated with transfusion of whole
blood, packed RBCs, and fresh frozen plasma
Result of donor leukoagglutinins causing recipientWBC aggregation, capillary leak, and acute respiratory distress syndrome
Usually resolves
No special selection of products is appropriatea donor
implicated in a transfusion-associated lung injury reaction is eliminated from the donor pool.
913
914
Transfusion-associated graft-versus-host disease

Nearly always fatal, results in multiorgan system failure in susceptible patients
Prevented by using gamma-irradiation of products
Immunomodulation
Controversial issues and analyses of results equivocal
May be reduced by using leukocyte-reduced products
Postoperative infectionsincreased incidence among
patients receiving transfusion who underwent surgery
Cancer recurrencecolorectal cancer studied most
Table 1. Transfusion of Cellular Components

Component
RBCs
Types
Packed RBCs
Special RBC products

Washed
915
Hematocrit 80%
~180 mL/unit
Saline washes (machine) remove
90% of WBCs, most platelets,
& 98% of plasma proteins
Hematocrit 65% (ultra-washed)
~180 mL/unit
High glycerol solution (40% w/v)
for storage
95% of WBCs, platelets, &
plasma proteins removed
Indications
Symptomatic anemia (e.g., angina, dyspnea,
postural hypotension, etc.)
Hb 7.0 g/dL
Hb <10 g/dL with acute myocardial infarction, unstable angina
Ongoing hemorrhageused alone if
estimated blood loss is 20%-50% total
blood volume
Above indications plus any of the following:
Anaphylactoid reactions
IgA or IgA subclass deficiency (presence of
anti-IgA antibodies)
Rare RBC types (McLeod phenotype, etc.)
Store autologous blood >42 days
Indications for washed RBCs (but more
expensive)
IV THERAPY
Frozen
Characteristics/unit
Hematocrit 70%-75%
~350 mL/unit
Infused at 2-4 mL/kg per hour
3% Hematocrit or 1 g/dL Hb
increment
225-250 mg iron (1 mg/cm3 of
RBC volume)
916
Table 1 (continued)
Component
RBCs (continued)
Types
Indications
Leukocyte-reduced
In US, <5 106 (by filtration)

In Europe, <1 106 (by
filtration)
~350 mL/unit
CMV-negative
Seronegative for CMV
Irradiated
Higher potassium content

Gamma radiation, 25 Gy
Nonhemolytic febrile transfusion reaction unresponsive to acetaminophen

Avoid HLA alloimmunization in nonsensitized
patients
Avoid transmission of new variant CJD prion
(speculative)
Prevent transmission of leukocyte-associated viruses
(CMV, HHV-8, EBV, HTLV)
Cross-match incompatibility
CMV-negative, immunodeficient hosts (bone marrow,
organ transplant recipients); leukocyte-reduced is
considered equivalent
Prevent transfusion-associated GVHD in
Immunodeficient patients (congenital immunodeficiencies, purine analogue-treated, not HIV,
or standard chemotherapy-treated malignancies)
Bone marrow, organ transplant recipients
Related donor or HLA-selected component
transfusion
Table 1 (continued)
Component
WBCs
Types
Granulocytes
irradiated
1
Collected by apheresis
0.1-0.3 109/L increment
Contains 3 1011/L platelets
1010/L,
Lymphocytes
Random-donor
pooled platelet
concentrates
5.5-7.5 1010/unit (60%-70%)

of whole blood unit platelets)
~50 mL dose1 U/10 kg body
weight (standard dose, 6 U)
917
Immunodeficient hosts with overwhelming

bacterial/fungal sepsis refractory to antimicrobials & recombinant granulocyte
colony-stimulating factor
and
Severe neutropenia <0.5 109/L
and
Prolonged marrow recovery anticipated
(>7-10 days)
Serious infection in patients with granulocyte dysfunction, e.g., CGD
Induce remission in CML patients with
molecular or cytogenetic relapse after bone
marrow transplant
Therapeutic transfusion in acute hemorrhage
in patients with thrombocytopenia
50 109/L
Prevent coagulopathy in massive transfusions
(150% of blood volume)
IV THERAPY
Platelets
Indications
918
Table 1 (continued)
Component
Platelets
(continued)
Types
Indications
Prophylactic transfusion in:
Treatment of acute leukemia patients with
platelet count 10 109/L*
Chemotherapy of solid tumor patients with
platelet count 10 109/L, except those with
bladder & necrotic tumors (threshold,
20 109/L)
Febrile or anticoagulated patients with platelet
count <20 109/L
Dental extraction, many invasive procedures, &
major operations if platelet count 50 109/L)
Reserve for serious bleeding in ITP; avoid in TTP,
heparin-associated thrombocytopenia unless bleeding
is life-threatening
Table 1 (continued)
Component
Platelets
(continued)
Types
Irradiated
Gamma radiation, 25 Gy
Single-donor
(apheresis)
>3 1011
~200 mL
10-50 109/L increment
Indications for random-donor platelet

concentrates plus the following:
Prevent transfusion-associated GVHD in:
Bone marrow, organ transplant
recipients
Severely immunodeficient or immunosuppressed patients
Related-donor or HLA-selected component transfusion
Histocompatible platelet transfusion for alloimmunized patients with active hemorrhage
919
Indications for random-donor platelet

concentrates plus either of the following:
Avoid HLA alloimmunization in
patients anticipated to have multiple
transfusions (e.g., AML at diagnosis)
during therapy to prevent refractoriness
to random-donor platelets or
Nonhemolytic febrile transfusion reaction unresponsive to acetaminophen
IV THERAPY
Leukocyte-reduced
Indications
920
Table 1 (continued)
AML, acute myelogenous leukemia; CGD, chronic granulomatous disease; CJD, Creutzfeldt-Jakob disease; CML, chronic myelogenous leukemia; CMV,
cytomegalovirus; EBV, Epstein-Barr virus; GVHD, graft-versus-host disease; HHV, human herpesvirus; HTLV, human T-lymphotropic virus; ITP, idiopathic thrombocytopenic purpura; TTP, thrombotic throbocytopenic purpura.
*Transfusion at higher levels may be necessary in patients with hemorrhage, high fever, hyperleukocytosis, rapid fall of platelet count, or coagulation
abnormalities (e.g., acute promyelocytic leukemia), and in those undergoing invasive procedures or in situations in which platelet transfusions may not be
readily available in case of emergencies.
Bone marrow aspirations and biopsies can be performed safely at counts <20 109/L.
Central nervous system operation may require >100 109/L.
Table 2. Transfusion of Plasma Derivatives

Derivative
Factors
All factors (fibrinogen, factors No RBCs, essentially

II, V, VII, VIII, IX, X, XI,
no platelets
XIII, proteins C & S, AT III) ~220 mL/unit
Dose: 10-20 mL/kg
(except warfarin reversal = 5-8 mL/kg)
Cryoprecipitate
vWF, factor VIII, fibrinogen,

factor XIII, fibronectin
Cryo-poor plasma
FFP factors except vWF
Indications
921
Hemorrhage in multiple coagulation factor

deficiency (e.g., liver disease)
Coagulopathy in factor XI, AT III, protein
C, protein S deficiency
Urgent reversal of warfarin therapy
Correction of known coagulation factor
deficiencies for which specific products
are not available
Coagulopathy in massive blood transfusion
(hemorrhage, PT & aPTT 1.5 control)
Used in TTP for plasma exchange when
cryo-poor plasma is not available
Transient reversal of platelet dysfunction in
~25 mL/unit
80-120 U factor VIII
uremic patients
150-200 mg fibrinogen Dysfibrinogenemia, hypofibrinogenemia
Infused at 200 mL/hour Replacement of factors when specific
Not virally inactivated
products are not available
Used in TTP apheresis (avoids transfusion
Supernatant of cryoprecipitate
of vWF)
AT, antithrombin; FFP, fresh frozen plasma; TTP, thrombotic thrombocytopenic purpura; vWF, von Willebrand factor.
IV THERAPY
FFP
922
Table 3. Special Coagulation Factor Products

Condition
Hemophilia A
Product
Recombinant factor VIII (Recombinate,
Kogenate, Bioclate, Helixate FS, Refacto)
Monoclonal antibody purified (Monoclate-P,
Hemofil M, Monarc-M)
DDAVP (1-desamino-8-D-arginine vasopressin, desmopressin)

Hemophilia B
Factor inhibitors
Recombinant factor IX (Benefix)

Monoclonal antibody purified (Mononine,
Alphanine SD)
Activated prothrombin complex concentrate
(Feiba [factor VIII inhibitor bypassing
activity], Autoplex T), NovoSeven recombinant factor VIIa
Porcine factor VIII (Hyate C)
Administration/indications
1 U/kg increases level by 2% (t1/2 = 8-12 hours)
Target activity level
Dental extraction prophylaxis: 50%-100%
Mild hemorrhage: 20%
Moderate hemorrhage: 30%-50%
Severe hemorrhage, surgery: 100%
Bolus before procedure
Continuous infusion during surgery, active hemorrhage
(4 U/kg per hour)
0.3 g/kg IV (median increment of 62% in factor VIII
activity)
Use for mild bleeding episodes
Intranasal: <50 kg-150 g, >50 kg-300 g
1.2 U/kg increases level by 1% (t1/2 = 24 hours)
1 U/kg increases level by 1% (t1/2 = 24 hours)
50-100 U/kg every 8-12 hours (not to exceed 200 U/kg daily)
Hemophilia A or B patients with factor inhibitors
100-150 U/kg (product ineffective if inhibitor level is >10
Bethesda U/mL)
Table 3 (continued)
Condition
von Willebrand disease
Product
DDAVP
Certain factor VIII products (e.g., HumateP, Koate-DVI or HP, Alphanate)
AT III deficiency
AT III
923
IV THERAPY
See above
For mild type 1 vWD
vWD types 2 and 3 respond poorly or variably
Contraindicated for vWD type 2B
Hemorrhage for which desmospressin is inadequate or inappropriate
Dose: 40-80 IU vWF:ristocetin cofactor
(RCoF)/kg every 8-12 hours, goal of vWF:RCoF
activity >50% (2-3 IU vWF/IU factor VIII)
1 U/kg increases level by 1%-2.1% (t1/2 = 2-4 days)
Dose: [Desired actual AT III % level] weight/1%
Desired level: 80%-120%
Replacement in congenital deficiency:
During major surgery, prolonged immobilization
Thrombosis during pregnancy (facilitate heparin)
Acute DVT or PE
Replacement in acquired deficiency:
Severe liver failure to prevent or control ICF
924
Table 3 (continued)
Condition
AT III deficiency
(continued)
Product
Hemorrhage in cirrhosis (prevent thrombosis or ICF
when factor IX is given)
Acute DVT or PE when AT III <70%
Surgery in those with disease associated with increased
AT III loss (e.g., nephrotic syndrome)
AT, antithrombin; DVT, deep venous thrombosis; ICF, intravascular coagulation and fibrinolysis (formerly termed DIC [disseminated intravascular coagulation]); PE, pulmonary embolism; vWD, von Willebrand disease; vWF, von Willebrand factor.
V INSIGHTS
EMERGENCY RESPONSE TEAM
RESPONSIBILITIES AND GUIDELINES
Edwin G. Wells III, M.D.
Nicola E. Schiebel, M.D.
EMERGENCY RESPONSE TEAM
Most medical centers have a team of physicians and other professionals designated to respond to medical emergencies,
such as cardiac arrest, in the hospital or outpatient clinics.
This team is the emergency response team or the code
team.
The assumption is that having a well-trained and prepared
team ready to respond to emergencies will improve the
outcomes of these situations.
For this goal to be realized, the team members must know
their respective roles and the protocols recommended for
handling medical emergencies so they can work together to
provide timely and appropriate care for patients in distress.
ERT LEADER RESPONSIBILITIES
Overall conduct of emergency situation (code); maintaining focus on medical priorities
Rhythm interpretation
Defibrillationearly defibrillation is highest priority
when indicated!
Pharmacologic therapy
Overseeing other team members performance
Basic life support (adequate cardiopulmonary resuscitation,
etc.)
Proper airway management (endotracheal tube placement,
etc.)
Special abbreviations used in this chapter: AHA, American Heart Association;

DNR, do not resuscitate.
925
Managing the scene of the emergency

Managing the many people who respond to codes is a
major challenge.
Anyone who does not have a defined role should be asked
to leave.
Look for someone to delegate this responsibility (e.g.,
nursing supervisor, charge nurse).
Managing patient transfer after resuscitation
Documenting the emergency and management in the medical record
Assisting the primary service in communicating with the
family
Special concerns
Over-response with loss of control at scene
Inadequate infection control precautions
Misunderstanding of do not resuscitate (DNR) policies
Poor documentation
Quality improvement issues
Family presence at sceneData suggest that this may be
acceptable, and even preferable, but only with adequate
attention from medical personnel.
MAYO DNR POLICYCONSULT INSTITUTIONAL

GUIDELINES
The following excerpt is quoted directly from the Mayo 2005
pocket calendar and the institutional procedural guidelines
(emphasis added):
1. A Do Not Resuscitate (DNR) order implements a decision
to withhold resuscitation in event of cardiac arrest. It is
an order to withhold treatment when and only when the
unresponsive patient has become clinically pulseless.
2. DNR refers to the withholding of the following treatments
in event of cardiac arrest:
1) endotracheal intubation and initiation of ventilatory
support,
2) chest compression,
3) electrical countershock,
4) external cardiac pacing, and
5) bolus administration of inotropes, vasopressors, or
antiarrhythmics.
Except in exceptional circumstances, these five therapies
926
V INSIGHTS
should be withheld together or potentially provided
together. Orders to provide some but not all potential therapies for cardiac arrest are strongly discouraged.
3. A DNR order may be compatible with maximum therapy. The patient may be receiving vigorous support in all
other therapeutic modalities and justifiably have a DNR
order. Some components of resuscitation (endotracheal
intubation, pacemaker placement, inotropic or vasopressor
infusions, antiarrhythmic therapy) may be given to a patient
with a DNR order who has not suffered cardiac arrest.
Decisions to withhold such treatments in nonarrest circumstances are often appropriate but must be made
consensually with the patient or surrogate and are not
encompassed by the DNR order.
4. A DNR order may be written by a physician involved in the
care of the patient:
after consultation with the patient or the appropriate
surrogate decision maker
and when, in the opinion of the patient or surrogate,
the burdens of the potential resuscitation outweigh the
anticipated benefits
5. The individuals involved in decision-making discussions
for implementation of a DNR order will vary depending on
the decision-making capacity of the patient:
For the patient with decision-making capacity, the decision shall be reached consensually by the patient and the
physician.
For the patient lacking decision-making capacity, and
who has been declared legally incompetent by the courts,
the decision shall be reached consensually by the courtappointed guardian and the physician.
For the patient lacking decision-making capacity who
has, by means of an Advance Directive, designated a
surrogate decision maker, the decision shall be reached
consensually by the designated surrogate and the
physician.
For the patient lacking decision-making capacity without
a designated surrogate decision maker, the decision shall
927
6.
7.
8.
9.
928
be reached consensually by the most appropriate surrogate decision maker and the physician. Typically, the
most appropriate surrogate decision maker will be a family member, or a consensus opinion of family members.
For the patient lacking decision-making capacity who
has an Advance Directive specifying a DNR status, a
DNR order will be written unless specifically rescinded by an appropriate surrogate.
In all circumstances, the decision should be consistent
with the patients values and desires.
A DNR order should not be implemented if the patient or
appropriate surrogate decision maker does not consent to
the order.
Parental/guardian approval is required for a DNR order
for a minor. The primary staff physician should talk with
the parents/guardians of the child and provide support to
the minor and parents/guardians in arriving at a decision.
A DNR order may be rescinded by the patient or appropriate surrogate at any time.
To the extent possible, a DNR order should be reviewed
with all involved parties when:
there is a change of physicians on the primary service
or another service assumes primary care of the patient.
the patient is taken from the patient care unit to a diagnostic or therapeutic procedure.
the patient is transferred to another patient care unit
(e.g., ICU to general care unit).
the patient undergoes a surgical operation or a procedure
requiring sedation. In the event a DNR order was
rescinded for surgery by the patient or appropriate surrogate, the perioperative resuscitation status and the
postoperative resuscitation status should both be clearly and distinctly documented in the medical record.
The surgical episode includes the anesthetic, operation,
and recovery time in postanesthetic care unit. The surgical episode ends when the patient is admitted to a
monitored or general care bed unless otherwise specified in the medical record. It may be appropriate for a
DNR order to stand during operation and anesthesia.
A nonrescinded do not intubate order is not appropriate for the patient undergoing general anesthesia.
V INSIGHTS
there is a significant change in the patients clinical
condition.
10. The primary (or co-primary) staff physician is responsible
for discussions with the patient or appropriate surrogate
regarding a DNR order. The staff physician may personally conduct these discussions or delegate this responsibility to a resident physician in training involved in the
care of the patient. However, other health team members
involved in the care of the patient (e.g., nurse, chaplain,
social worker) may participate in the discussions and decision-making process.
11. Careful considerations must be given to a patients Advance
Directives. Clarification should be sought from the patient
or appropriate surrogate regarding any ambiguity introduced by such a document, and the physicians should document the clarification in the chart.
12. Conflicts may arise in arriving at a DNR order. In such an
event, institutional resources available to assist in identifying
the underlying issues creating the conflict and to facilitate
the decision-making process include the Hospital Ethics
Consultation Service, Resuscitation Committee, Mayo
Clinical Ethics Council, and Legal Department.
EMERGENCY RESPONSE ALGORITHMS
The following algorithms (Fig. 1-9) are based on the 2000
American Heart Association (AHA) guidelines for advanced
cardiac life support. Every effort has been made to ensure
accuracy; however, these adaptations have not been officially reviewed by the AHA, and no guarantee can be inferred
that they reflect the intent of the AHA or any subsequent
revisions to the official guidelines.
929
Unresponsive patient
1.
2.
A
B
C
D
Primary survey:
Activate emergency response team
Call for defibrillator
Assess breathing (position airway)
Give 2 slow breaths (if no breathing)
Start chest compressions (if no pulse)
Attach monitor/defibrillator
No pulse
No pulse
Attempt defibrillation
3 shocks if VF/VT
persists
Follow VF/VT
algorithm
Continue CPR
Assess rhythm
VF/VT
Asystole/
PEA
Pulse restored
Continue CPR
Follow appropriate
algorithm
Support & observe

No pulse
Continue CPR
Secondary survey:
A Airway: attempt to place airway device
B Breathing: confirm and secure airway device, ventilation, oxygenation
C Circulation: IV access, adrenergic agent; consider antiarrhythmics,
buffers, pacing
D Differential diagnosis: search for and treat reversible causes
Non-VF/VT Epinephrine 1 mg IV, repeat every 3-5 minutes
VF/VT Vasopressin 40 units IV once or
Epinephrine 1 mg IV, repeat every 3-5 minutes
Fig. 1. Comprehensive emergency care algorithm. CPR, cardiopulmonary resuscitation; PEA, pulseless electrical activity; VF, ventricular fibrillation; VT, ventricular tachycardia.
930
V INSIGHTS
ABCD survey
Is patient's life at risk
Vitals
Level of consciousness
Unstable
Assess BP, HR, RR, & level
of consciousness
Stable
Unstable
Have at bedside:
O2 saturation monitor, IV line,
intubation equipment
Determine if instability is
related to tacyhcardia (rarely
if HR <150)
A fib/
A flutter
Narrow complex
tachycardia
Stable wide
complex tachycardia
See A fib/
A flutter
algorithm
Attempt Dx with 12lead ECG
Attempt Dx with 12lead ECG
Treat
Vagal maneuvers
Adenosine 6-mg IV
push
Treat
Stable VT or SVT
(see algorithm)
Unknownconsult
cardiology, consider
DC cardioversion
or amiodarone
Determine rhythm
V fib/VT
(see algorithm)
PSVT/A fib/A flutter

Synchronized cardioversion
100 J, 200 J, 300 J, 360 J
If unsuccessful, determine
heart function
Preserved function
-Blocker, calcium
channel blocker, digoxin
Amiodarone, sotalol,
procainamide
EF < 40% or CHF:

Digoxin
Amiodarone
Diltiazem
Fig. 2. Tachycardia algorithm. A, atrial; BP, blood pressure; CHF, congestive heart failure; Dx, diagnosis; EF, ejection fraction; fib, fibrillation; HR, heart rate; PSVT, paroxysmal supraventricular tachycardia;
RR, respiratory rate; SVT, supraventricular tachycardia; VT, ventricular tachycardia.
931
932
Rule out WPW

If confirmed atrial
fibrillation/atrial flutter
Anticoagulation
Known onset <48 hours
Known onset >48 hours
Immediate electrical cardioversion 50 J,

100 J, 200 J
(Atrial flutter, start at 25 J)
Control rate
Anticoagulate
Convert rhythm
If unsuccessful
Control rate
Diltiazem 0.25 mg/kg IV over 2 minutes
Metoprolol 5 mg IV every 5 minutes x 3
Control rate
Diltiazem 0.25 mg/kg
over 2 minutes
Metoprolol 5 mg IV every 5 minutes x 3
Convert rhythm
Amiodarone 800-1,600 mg PO daily
x 1-3 weeks
Procainamide 100 mg IV every 5-10
minutes until QRS widens 50% or
maximum dose (1.5 g)
Propafenone 150 mg PO every
8 hours; maximum dose, 900 mg/day
Anticoagulate
Heparin 80 U/kg IV bolus, then 18
U/kg per hour IV infusion for 3 weeks
Delayed electrical or chemical

cardioversion
Fig. 3. Atrial fibrillation/atrial

flutter algorithm. WPW, WolffParkinson-White syndrome.
Synchronized DC cardioversion always is option
Polymorphic
Monomorphic
No clinical heart failure

Procainamide
Sotalol
Amiodarone
Lidocaine
No clinical heart failure
Cardiac function impaired

JVP
S3
Edema/rales
Assess QT interval
Long QT
Normal QT
Amiodarone 150-mg IV bolus over 10 minutes

Lidocaine 0.5-0.75 mg/kg IV push
Synchronized cardioversion
Treat ischemia
Correct electrolyte(s)
-Blockers or
lidocaine or
amiodarone
Fig. 4. Stable ventricular tachycardia
933
algorithm. JVP, jugular venous pressure; S3, third heart sound.
V INSIGHTS
Correct electrolytes
Magnesium
Overdrive pacing
Primary ABCD survey

Focus: basic CPR & defibrillation
Check responsiveness
A Airway: open the airway
B Breathing: provide positive-pressure ventilations
C Circulation: give chest compressions
D Defibrillation: assess for & shock VF/pulseless VT
up to 3 times (200 J, 300 J, 360 J) if necessary
Check rhythm
Still VF/VT, continue CPR
A
B
B
B
C
C
C
D
Secondary survey
Airway: place
Breathing: confirm
Breathing: secure
Breathing: adequate?
Circulation: IV access
Circulation: identify rhythm
Circulation: appropriate drugs
Differential diagnosis: find cause
Resume defibrillation
Epinephrine 1-mg IV push

(repeat every 3-5 minutes)
or
Vasopressin 40 U IV
(one dose only)
Defibrillate 1 x 360 J
within 30-60 seconds
Consider antiarrhythmics
Amiodarone 300 mg IV push,
repeat 150 mg in 5 minutes,
max = 2.2 g IV/24 hours
Lidocaine 1 mg/kg IV, may
repeat in 5 minutes, max = 3 mg/kg
Magnesium sulfate 1-2 g
(2-4 mL of 50% solution) in 10 mL
D5W IV push
Procainamide 20 mg/minute IV
max = 17 mg/kg
Fig. 5. Ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) algorithm. CPR, cardiopulmonary resuscitation; D5W, 5% dextrose in water; max, maximum dose.
934
V INSIGHTS
Absolute bradycardia = HR <60 or HR
less than expected for underlying condition
Primary ABCD survey (Fig. 5)
Ensure defibrillator is available
Secondary ABCD survey (Fig. 5)
Is the patient unstable?
Is bradycardia the cause?
Check vitals, O2, ECG, chest X-ray,
focused history & physical
Unstable
Stable
Atropine 0.5-1.0 mg
Transcutaneous pacing
Dopamine 5-20 g/kg
per minute
Epinephrine 2-10 g/
minute
If neither,
observe
Differential diagnosis:
Type II 2 AV block
or
3 AV block
Transcutaneous pacing until
transvenous pacing available
Fig. 6. Bradycardia algorithm. AV, atrioventricular; HR, heart rate.
935
PEA = rhythm on monitor, no palpable pulse
Primary ABCD survey

A
B
B
B
C
C
C
C
D
Secondary ABCD survey

Focus: more advanced assessments & treatments
Airway: place airway device
Breathing: confirm airway device
Breathing: secure airway device
Breathing: confirm effective oxygenation & ventillation
Circulation: establish IV access
Circulation: identify rhythm
monitor
Circulation: administer drugs appropriate for rhythm & condition
Circulation: assess for occult blood flow ("Pseudo PEA")
Differential diagnosis: find cause, treat it
Find cause
Most frequent causes of PEA = 5 Hs & 5 Ts
Hypoxia
Tablets (drug overdose, accidents)
Hypovolemia
Tamponade
Hypo/hyperkalemia
Hypothermia
Thrombosis, coronary (ACS)
Hydrogen ion excess
Thrombosis, pulmonary (embolism)
acidosis
Treat
Treat
underlying
cause
Epinephrine 1-mg IV
push, repeat every
3-5 minutes
Atropine 1 mg IV
(if PEA rate is slow),
repeat every 3-5
minutes to total dose
of 0.04 mg/kg
Fig. 7. Pulseless electrical activity (PEA) algorithm. ACS, acute

coronary syndrome; CPR, cardiopulmonary resuscitation; VF, ventricular fibrillation; VT, ventricular tachycardia.
936
V INSIGHTS
Primary ABCD survey
C Circulation: confirm true asystole
Rapid scene survey: is there any evidence that personnel should
not attempt resuscitation (e.g., DNR order, signs of death)?
A
B
B
C
C
C
C
D
Secondary ABCD survey

Focus: more advanced assessments & treatments
Airway: place airway device as soon as possible
Breathing: confirm airway device placement by exam plus
confirmation device
Breathing: confirm effective oxygenation & ventilation
Circulation: confirm true asystole
Circulation: establish IV access
Circulation: identify rhythm monitor
Circulation: give medications appropriate for rhythm & condition
Differential diagnosis: search for & treat identified reversible causes
Treat
Transcutaneous
pacing
Perform immediately
Epinephrine 1-mg
IV push, repeat every
3-5 minutes
Atropine 1 mg IV,
repeat every 3-5
minutes to 0.04
mg/kg
When to stop?
Successful resuscitation
Support & observe
Persistent asystole
Consider:
Quality of resuscitation
Atypical clinical features
present?
Support for cease-efforts
protocols in place?
Fig. 8. Asystole algorithm. CPR, cardiopulmonary resuscitation;

DNR, do not resuscitate; VF, ventricular fibrillation; VT, ventricular
tachycardia.
937
938
Find time of onset
>
_ 48 hours
<48 hours
Preserved cardiac
function
Heart failure
DC cardioversion
(recommended) or
one of the following:
Amiodarone
Flecainide
Procainamide
Propafenone
Sotalol
Urgent
hemodynamic
instability
IV heparin
TEE to exclude
atrial clot
Nonurgent
Anticoagulation for
3 weeks (PT INR
2-3)
Cardioversion
Cardioversion
Anticoagulation
for 4 weeks
DC cardioversion
(recommended)
or
Amiodarone
Anticoagulation
for 4 weeks
Avoid adenosine, -blockers, calcium channel blockers, and digoxin
Fig. 9. Atrial fibrillation/flutter with WolffParkinson-White syndrome algorithm.
V INSIGHTS
END OF LIFE
Anna M. Georgiopoulos, M.D.
Casey R. Caldwell, M.D.
GOALS OF PALLIATIVE CARE

Palliative care involves shifting efforts from an attempt to
cure disease to relief of symptoms and improvement of quality of life. Hospice care is a multidisciplinary approach to
palliative care of the dying patient and family. Palliative
and hospice care may be provided at home or in a hospital,
a nursing home, or a dedicated hospice facility.
Many losses can accompany terminal illness. Patients social
and financial status, their relationships with friends and family, and their ability to independently perform activities of
daily living often change as illness progresses. Symptoms
causing distress for patients with advanced disease include
pain, dyspnea, weakness and fatigue, insomnia, loss of alertness or confusion, depression and anxiety, anorexia and
cachexia, nausea and vomiting, and constipation.
Multiple effective therapies are available to manage patients
physical and mental suffering at the end of life. In the time
leading up to death, patients may draw hope from deepening
their relationships and spirituality, bringing a sense of closure
to their lives, and finding meaning in their achievements and
legacies.
MEDICAL DECISION MAKING
To consent to a proposed course of care, a patient must be able
to demonstrate understanding of the risks, benefits, and alternatives of the plan and to reasonably evaluate this information and communicate his or her decision. A health proxy is
someone appointed by a patient to make health care decisions when the patient is no longer able to do so. The most
useful advance directives designate a health proxy who knows
the patient well and has talked to the patient about his or her
939
goals and values. Long lists of acceptable and unacceptable

medical interventions may unnecessarily constrain care, and
vague statements (no heroic measures) may be difficult
to interpret when tough decisions need to be made. Find
out what the laws are in your state for surrogate decision
making when a patient does not have advance directives
appointing a health proxy.
Conflicts between medical personnel and family members
over medical futility and withdrawal of support often come
down to issues of communication and trust. It may help for
both the family and medical team to appoint one person as the
primary contact and to schedule regular communications.
The types of questions patients and families have and the
level of detail they desire to know may vary. Remember that
the goals of care are set by the patient or the patients proxy,
but that rational decision making about the best way to pursue those goals is more likely to occur when the medical team
provides appropriate information in an empathetic manner.
SYMPTOM CONTROL
Pain Management
Medications for specific pain syndromes are listed in Table 1.
Opioids are the mainstay of care for severe pain at the end of
life. As long as there is informed consent, it is ethically and
legally acceptable to use doses of opioids necessary to control a patients suffering, even if this may unintentionally
hasten his or her death. This is known as the principle of
double effect.
There is no upper dose limit for opioids, but be careful
with adjuvants such as acetaminophen or NSAIDs. You
may want to separate the opiate from the adjuvant.
For example, rather than risk acetaminophen overdose in
patients with moderate pain by using Percocet, prescribe
Tylenol 1,000 mg every 6 hours on a scheduled basis, sustained release oxycodone (OxyContin), 10 mg every 12
hours, and rapid release oxycodone, 5-10 mg every 4
hours, for breakthrough pain.
Balance alertness and pain control in accordance with patient
and family values and goals. An exhausted patient sleeps a
lot but is alert between naps, whereas a sedated patient cannot be fully awakened.
940
Table 1. Medications for Specific Pain Syndromes

Burning, tingling
neuropathic pain
Shooting, stabbing,
electrical neuropathic pain
Gabapentin100 mg PO tid, escalate every 1-2 days by 100 mg

PO tid, up to 3,600 mg/day or more
Desipramine10-25 mg
Carbamazepine100 mg
PO qhs, increase every
PO bid-tid, increase by
4-7 days
100-200 mg every 5-7 days
Valproic acid250 mg PO
qhs, increase 250 mg every
7 days in divided doses
Bowel obstruction
(inoperable)
Opioids
NSAIDs
Dexamethasone2-20 mg daily (also for capsular liver
pain)
Pamidronate90-120 mg
Scopolamine0.1-0.4 mg
IV every 4-6 weeks
SQ/IV every 4 hours or
Calcitonin200 IU or
transdermal patches 1-3
nasally daily-bid
every 3 days or 10-80
Radiation
g/hour IV/SQ infusion
Orthopedic interventions,
Octreotide100 g SQ
braces
every 8-12 hours or 10
g/hour IV
941
V INSIGHTS
bid, twice daily; qhs, at bedtime; tid, 3 times daily.
Bone pain
If the patient has opiate-induced delirium or respiratory

depression (<6 breaths/minute), opiates may be reversed
with naloxone, 0.1-0.2 mg IV every 1-2 minutes until
alert. Monitor and repeat as needed. This should rarely
be necessary.
If the patient requires increasing doses of pain medications,
disease progression is a more likely explanation than drug
tolerance.
Dying patients with a history of substance abuse still deserve
adequate pain control.
Urticaria and pruritis occurring with opioids are usually due
to mast cell destabilization, not true drug allergy. Try fexofenadine 60 mg PO twice daily or doxepin 10-30 mg PO at
bedtime.
Treat drug-associated nausea, vomiting, and constipation
aggressively rather than compromise pain control. Consider
a psychostimulant to combat sedation.
All opioids that can be given IV can also be given SQ, even in
continuous infusion. This may be preferable to IM dosing,
which is painful. Do not forget liquid preparations or administration to buccal mucosa (oral morphine elixir).
Also consider rectal administration, transdermal patches,
or insertion of a feeding tube to deliver pain medications.
Consider nonpharmacologic approaches such as transcutaneous electrical nerve stimulation, acupuncture, heat, cold,
relaxation therapy, music, or massage.
Refer to specialists for persistent pain or consideration of
nerve blocks or other procedures if acceptable to patient.
Depression and Anxiety

Medications for depression or anxiety are listed in Table 2.
Major depression and hopelessness are not normal or
inevitable consequences of serious illness; they increase
patients suffering and may shorten life.
If you feel depressed around the patient, consider that the
patient may be depressed.
Physical symptoms such as altered sleep, appetite, and energy are less useful for the diagnosis of depression in patients
at the end of life.
Simply asking, Are you depressed? is a quick, accurate
way to screen for depression in this population.
942
Table 2. Medications for Depression or Anxiety

Class of agent
Comments
Drugs of choice for depression:
quick response, often in 24 hours
May stimulate appetite
Increase dose if tolerance develops
Can precipitate delirium
SSRIs
Treat both depression & anxiety

Response in 2-4 weeks
Tricyclic antidepressant
Only if also needed for pain

control, insomnia, appetite
stimulation
Some effect on anxiety
Methylphenidatestart 2.5-5 mg bid (8 AM & noon),

titrate daily, up to 20 mg bid; extended-release
available
Dextroamphetaminestart 2.5-5 mg PO bid, up to
20 mg bid; extended-release available
Pemoline18.75-37.5 mg PO every AM, up to 75
mg bid; chewable SL form available
Fluoxetine2.5-5 mg PO qhs, increase weekly up to
80 mg/day
Paroxetine10-60 mg PO qhs
Sertraline25-200 mg PO daily
Citalopram20-40 mg PO daily
Nortriptyline10-125 mg PO daily
Desipramine12.5-150 mg PO daily
943
V INSIGHTS
Psychostimulant
Examples
944
Table 2 (continued)
Class of agent
Comments
Other
Mixed depression & anxiety
Benzodiazepine
Anxiety
Examples
Mirtazapinestart 7.5 mg PO qhs, up to 15-60 mg qhs
(sedating, stimulates appetite)
Nefazodone100-300 mg PO bid (sedating)
Venlafaxine18.75 mg PO bid, up to 187.5 mg bid
Diazepam2-10 mg qhs-tid
Clonazepam0.25-2 mg daily-bid
Lorazepam0.25-2 mg PO/SL tid-qid
bid, twice daily; qhs, at bedtime; qid, 4 times daily; SL, sublingual; SSRI, selecive serotonin reuptake inhibitor; tid, 3 times daily.
V INSIGHTS
Anhedonia, irritability, helplessness, hopelessness, worthlessness, excessive guilt, intractable pain, and suicidal
ideation are also suggestive of depression.
Asking about suicidal ideation does not increase the risk of
suicide.
A combination of counseling/psychotherapy and medications is optimal for severe mood disorders.
Benzodiazepines may worsen memory or precipitate confusion. Consider antipsychotics for these patients.
Look for medications that may worsen depression (-blockers) or anxiety (albuterol nebulizer, caffeine).
Delirium
Neuroleptics are listed in Table 3.
Look for underlying reversible cause; decide how far to look
in accordance with goals.
Day-night reversal may be first sign of delirium in patients
nearing death.
Consider antipsychotic medications and benzodiazepines.
Severely agitated, delirious patients nearing death may benefit from high-dose infusion of benzodiazepines, propofol, or
barbiturates.
Dyspnea
Many effective therapies are available for managing dyspnea
at the end of life (Table 4).
Table 3. Neuroleptics
Agent
Dose
Haloperidol
0.5-1 mg PO, IV, SQ every 1

hour as needed, then every
6-12 hours to maintain (1-20
or more mg/day)
Risperidone (fewer extrapyramidal 0.5-1 mg every 12 hours &
effects)
titrate
Olanzapine (fewer extrapyramidal 2.5-7.5 mg PO every 12 hours
effects)
945
Empiric management of dyspnea is outlined in Table 5.
Nausea
Medications for nausea are listed in Tables 6 and 7.
Constipation
Medications for constipation are listed in Table 8.
Prescribe stimulant laxatives prophylactically for patients
taking opioids.
Stool softeners or dietary changes alone are unlikely to
be effective.
Table 4. Specific Management of Dyspnea

Cause
Bronchospasm
Thick secretions
Good cough
Poor cough
Anemia
Aspiration
Airway obstruction
SL, sublingual.
946
Therapy
Nebulized albuterol 2.5-5 mg and/or
ipratropium 0.125 mg every 4 hours
Dexamethasone2-20 mg PO, IV, SQ
daily
Nebulized saline
Guaifenesin
Scopolamine0.1-0.4 mg SQ/IV every
4 hours or 1-3 transdermal patches every
3 days or continuous IV/SQ infusion
Glycopyrrolate0.4-1 mg daily SQ
infusion or 0.2 mg SQ/IV every 4-6
hours as needed
Hyoscyamine0.125 mg PO/SL every 8
hours
Transfuse to >10 g/dL hemoglobin, repeat
if provides symptomatic relief
Erythropoetin (epoetin alfa)10,000 IU
SQ 3 times weekly if life expectancy is
several months, increase as needed
Thicken foods
Nebulized racemic epinephrine
Dexamethasone2-20 mg PO, IV, SQ
daily
Oxygen-helium mixture
Surgery, radiation if in accordance with
patient goals
Table 5. Empiric Management of Dyspnea

Opioids
Follow subjective breathlessness, not arterial blood

gases or oxygen saturation
Mild dyspneaacetaminophen 325 mg/codeine

30 mg PO every 4 hours
plus breakthrough dose
30 mg codeine every 2
hours
Severe dyspneamorphine
5-15 mg PO every 4
hours, titrate
SL, sublingual.
Dopamine blockers
Chlorpromazine or promethazine has had anecdotal
success when used in conjunction with opioids
Use in same doses as for
nausea (Table 6)
Anxiolytics
Lorazepam0.5-2 mg PO, SL,
IV hourly as needed, then
every 4-6 hours to maintain
Clonazepam0.25-2 mg PO
every 12 hours
947
V INSIGHTS
Oxygen
948
Table 6. Medications for Nausea

Class of medication
Try in these conditions
Cerebral/liver metastases
Opioid or other medication side effect
Chemotherapy
Metabolichypercalcemia, hyponatremia,
liver/kidney failure
CHF/ischemia
Opioid or other medication side effect
CHF/ischemia
Movement-induced nausea
Bowel obstruction
Failure of other agents (expensive)
Chemotherapy
Cerebral/liver metastases
Meningeal irritation
Chemotherapy
Antihistamines
Anticholinergics
Serotonin antagonists
Corticosteroids
bid, twice daily; CHF, congestive heart failure; tid, 3 times daily.
Examples
Haloperidol0.5-2 mg PO, IV, SQ every 6 hours, then
titrate (less sedating)
Metoclopramide10-20 mg PO every 6 hours
Droperidol2.5-5 mg IV every 6 hours
Diphenhydramine25-50 mg PO every 6 hours

Meclizine25-50 mg PO every 6 hours
Hydroxyzine25-50 mg PO every 6 hours
Scopolamine0.1-0.4 mg SQ/IV every 4 hours or
1-3 transdermal patches every 3 days
Ondansetron8 mg PO tid
Granisetron1 mg PO daily-bid
Dexamethasone6-20 mg daily PO, IV, or IM
V INSIGHTS
Table 7. Additional Antinausea Agents
Class of
agent
Prokinetic
Antacids
Cytoprotective
Anxiolytic
Try in these
conditions
Example
Opioid side effect Metoclopramide10-20 mg

Ileus
PO every 6 hours
Hyperacidity
Maalox2 Tb every 2 hours
GERD
as needed
Famotidine20 mg PO/IV
or other H2 blocker
Omeprazole20 mg PO
daily-bid or other proton
pump inhibitor
Gastric irritation Misoprostol200 g
from NSAIDs
bid-qid
Omeprazole20 mg PO
daily-bid or other proton
pump inhibitor
Nausea associated Lorazepam0.5-2 mg PO
with anxiety
every 4-6 hours
Tetrahydrocannabinol2.55 mg PO tid
bid, twice daily; GERD, gastroesophageal reflux disease; qid, 4 times daily;
Tb, tablespoon; tid, 3 times daily.
Bulking agents such as psyllium can exacerbate constipation in patients with poor fluid intake and immobility.
Use a maximum dose before deciding that an agent is
ineffective.
Look for medications that may be contributing (calcium
channel blockers, tricyclic antidepressants), and look for
causes such as dehydration.
Diarrhea
Medications for diarrhea are listed in Table 9.
Consider dietary modifications.
Look for easily treatable causes.
Monitor for perianal skin breakdown.
949
950
Table 8. Medications for Constipation

Peristaltic stimulants
Prune juice120-240 mL
daily-bid
Senna1-2 tablets PO
qd-bid (or cascara
sagrada 4-12 mL qhs)
Bisacodyl5 mg PO/PR
qhs, titrate
Osmotic agents
Lactulose30 mL PO
every 4-6 hours, titrate
Sorbitol30 mL 70%
every 2 hours until
results
Milk of magnesia1-2
tablets daily-tid
Magnesium citrate1-2
bottles as needed
bid, twice daily; PR, rectally; qd, daily; qhs, at bedtime.
Stool softeners
Docusate sodium50100 mg PO bid
Fleet enemaas needed
Warm soapy enema (also
induces peristalsis)
Prokinetic agents
Lubricants/irritants
Metoclopramide10-20
mg PO every 6 hours
Glycerin suppositories
Mineral oil
V INSIGHTS
Anorexia and Weight Loss
Appetite stimulants are listed in Table 10.
Family and friends may be more distressed than patient is
about poor appetite and cachexia.
Discontinue dietary restrictions. Experiment with different
foods.
Patients typically stop oral intake in the last days to hours of
life.
Dehydration and ketosis may stimulate endorphin production
and often are not uncomfortable for patients at the end of
life.
Dry mouth can be combated by good oral care and is not
likely to improve with IV fluids.
In some cases, delirium may respond to IV hydration; this is
unlikely in terminal delirium.
Feeding tubes are associated with risk of infection and aspiration, discomfort, and occasional need for restraints.
IV fluids and total parenteral nutrition may worsen ascites,
peripheral edema, and pulmonary edema and may not prolong life in a terminal setting.
Table 9. Medications for Diarrhea

Diarrhea
Mild/transient
Moderate
Severe
Attapulgite30 mL
or 2 tablets as
needed
Bismuth salts1530 mL bid-qid
Loperamide2-4
mg PO every 6
hours or more
Diphenoxylateatropine2.5-5
mg PO every 6
hours or more
Tincture of
opium0.7 mL
PO every 4 hours
or more (may
cause delirium)
Octreotide50 g
SQ every 8-12 hours,
up to 500 g SQ
every 8 hours or
more, or continuous
SQ/IV infusion
10-80 g/hour
IV fluid support if
in accordance with
patient goals
bid, twice daily; qid, 4 times daily.

951
Table 10. Appetite Stimulants

Drug
Dexamethasone2-20 mg
PO every AM
Megestrol acetate200 mg
PO every 6-8 hours, titrate
to effect
Tetrahydrocannabinol
Psychostimulantsmethylphenidate, dextroamphetamine, pemoline
Comments
Side effects less of concern in
patients with short life expectancy
Other steroids may be used
Reduce appetite in healthy population but may increase it at end of

life
See Table 2 for dosing
Androgensoxandrolone,
nandrolone
Fatigue and Weakness

Consider corticosteroids and psychostimulants.
Good hygiene, frequent turning, hydrocolloid dressings, and
air mattresses may help prevent skin breakdown and pressure
ulcers.
Active or passive range of motion and massage on intact
skin may also help.
Insomnia
Medications for insomnia are listed in Table 11.
Use extended-release medications for pain control overnight.
Use good sleep hygienehave patient maintain a regular
schedule; avoid alcohol, caffeine, and nicotine; and stay out
of bed when awake.
Consider the contribution of medications such as bronchodilators or corticosteroids to insomnia.
952
V INSIGHTS
Table 11. Medications for Insomnia
Class of drug
Example
Comments
Antihistamines
Diphenhydramine
25-50 mg PO qhs
Lorazepam0.5-2
mg PO qhs
Tolerance is common
Anticholinergic effects
May worsen or precipitate dementia or
delirium
May help day-night
reversal or delirium
Less daytime sedation
Benzodiazepines
Sedating
neuroleptics
Other options
Chlorpromazine
10-25 mg qhs
Trazodone25-200
mg PO qhs
Zolpidem5-10 mg
PO qhs
Fewer side effects
qhs, at bedtime.
953
V INSIGHTS
EPONYMS IN INTERNAL MEDICINE
John B. Bundrick, M.D.
A
Abadie signspasm of the levator palpebrae superioris in
thyrotoxicosis.
Addison diseaseautoimmune chronic adrenal insufficiency.
Adie pupilone pupil larger than the other; both show slow
or no reaction to light and accommodation (also called tonic
pupil).
Adson maneuverpalpation of the radial pulse with elevation of the chin and rotation of the head to the side contralateral
to the pulse palpated demonstrates decrease in amplitude of
the pulse and indicates thoracic outlet syndrome.
Albright syndromehereditary osteodystrophy-pseudohypoparathyroidism.
Allen testtest of arterial supply to the hand, observing color
change with sequential compression of the radial and ulnar
arteries.
Alport syndromeautosomal dominant hereditary nephritis
and neural hearing loss.
Alzheimer diseaseslowly progressive degenerative cortical
dementia.
Anton syndromeblindness, denial of blindness, and
confabulation.
Argyll Robertson pupilpupil accommodates but does not
react to light; seen with syphilis, Wernicke encephalopathy,
and diabetes mellitus.
Arnold-Chiari malformationcongenital occipital bone and
proximal spine malformation causing displacement of cerebellar tonsils into cervical canal, resulting in hydrocephalus,
papilledema, cranial nerve palsies, and cerebellar ataxia. Often
associated with spina bifida and meningocele.
955
Aschoff bodiesendocardial granuloma pathognomonic for

rheumatic fever.
Auer bodiesrod-shaped inclusions seen at microscopy in
acute myeloid leukemia.
Austin Flint murmurfunctional late diastolic murmur simulating mitral stenosis in severe aortic regurgitation.
Austrian syndromepneumococcal pneumonia, endocarditis, and meningitis.
B
Babinski signhyperextension of the big toe after lateral plantar stimulation; indicative of upper motor neuron disease.
Bainbridge reflexincreased heart rate due to increased right
atrial pressure.
Baker cystposterior enlargement and herniation of the
popliteal bursa.
Banti diseaseportal hypertension with congestive
splenomegaly, hypersplenism, and anemia.
Barlow syndromemitral valve prolapse murmur and chest pain.
Barrett esophaguscolumnar metaplasia of distal esophagus secondary to long-standing reflux.
Bartholin cystinflammation of Bartholin gland near the
introitus of the vagina.
Bartter syndromehypokalemic alkalosis, hyperaldosteronism, and normal blood pressure.
Basedow (Graves) diseasethyrotoxicosis.
Batista procedureleft ventricular myomectomy with mitral
valvuloplasty in patients with end-stage dilated cardiomyopathy in an attempt to restore ventricular geometry, Frank-Starling
curve, and function.
Battle signretroauricular ecchymosis indicating fracture of
the base of the skull.
Bazex syndromeparaneoplastic acrokeratosis affecting ears,
nose, hands, and feet and associated with laryngeal and
esophageal cancer.
Beau linestransverse lines in fingernails resulting from nail
growth interruption as a result of severe systemic illness.
Beck triadhypotension, increased jugular venous pressure,
and absence of apex beat, with pericardial tamponade.
Behet syndromeoral and genital ulcers, pyoderma, uveitis.
956
V INSIGHTS
Bekhterev diseaseankylosing spondylitis.
Bell palsyunilateral lower motor neuron paralysis of cranial
nerve VII (facial nerve).
Bence Jones proteinmonoclonal light chains of IgG seen
in urine of patients with multiple myeloma.
Berger diseaseIgA nephropathy.
Bernard-Soulier syndromethrombocytopenia, congenital
giant platelets, bleeding diathesis, and platelet dysfunction due
to lack of glycoprotein Ib.
Bernheim syndromebulging of the interventricular septum
into the right ventricle as a result of increased left-sided pressures, causing right ventricular failure.
Bezold reflexvagal reflex causing bradycardia, hypotension,
syncope, and nausea after inferior wall infarction.
Bezold-Jarisch reflexvagal hyperstimulation usually following an inferior myocardial infarction, with hypotension and
bradycardia.
Billroth operationI, removal of distal stomach with endto-end anastomosis with duodenum; II, gastroduodenal anastomosis with duodenal closure.
Binswanger diseasepremature atherosclerotic vascular
dementia characterized by memory loss, paranoia, and emotional lability.
Blackfan-Diamond syndromerare, progressive, hematologic disorder that presents in early childhood as a normocytic and normochromic aplastic or hypoplastic anemia and results
from defective erythropoiesis and lack of nucleated erythrocytes in the bone marrow.
Blumberg signrebound tenderness indicating peritoneal
inflammation.
Blumer shelfmetastatic gastric cancer to the pelvic floor
palpable on rectal examination.
Boerhaave syndromeesophageal rupture as a result of repetitive vomiting.
Bouchard nodeshard nodular deformity of the proximal
interphalangeal joints, pathognomonic for osteoarthritis.
Bourneville diseasetuberous sclerosis, characterized by adenoma sebaceum, seizures, and mental retardation.
957
Bouveret syndromegiant gallstone erodes into the duodenum

and causes intestinal obstruction and gastrointestinal tract bleeding.
Bowen diseaseintraepidermal epithelioma, with 15%-30%
incidence of malignancy.
Bradbury-Eggleston syndromeidiopathic orthostatic
hypotension, primary autonomic failure.
Branham signbradycardia caused by compression of hemodynamically important arteriovenous fistula.
Bright diseasechronic nephritis.
Broadbent signsystolic retraction of the ictus cordis as a
result of constrictive pericarditis.
Broca aphasiamotor aphasia (i.e., person understands but
cannot produce words).
Brown-Squard syndromeipsilateral flaccid paralysis and
impairment of touch, position, and vibration sense, with contralateral loss of pain and temperature from a lesion affecting
one-half of the spinal cord.
Brudzinski signflexion of neck results in flexion of hip and
knee, indicates meningeal inflammation.
Brugada syndromehereditary disorder characterized by right
bundle branch block, ST-segment elevation, and sudden death.
Budd-Chiari syndromesuprahepatic vein thrombosis, with
jaundice, ascites, and portal hypertension.
Buerger diseasethromboangiitis obliterans.
Burkitt lymphomamost rapidly progressive human tumor,
a rare type of non-Hodgkin lymphoma.
C
Caplan syndromepneumoconiosis (typically silicosis) with
Carey Coombs murmurmid-diastolic murmur heard during acute rheumatic fever and indicative of carditis.
Carney complex or syndromeautosomal dominant condition characterized by spotty pigmented skin lesions with atrial myxomas, psammomatous melanotic schwannoma, and
Cushing syndrome.
Caroli diseasecongenital biliary tree ectasia with biliary
cyst formation.
Carvallo signincrease in tricuspid regurgitation murmur
with deep inspiration.
958
V INSIGHTS
Castleman diseaseangiofollicular lymph node hyperplasia,
a lymphoma variant.
Chaddock reflexnoxic stimulus of lateral malleolus produces extension of great toe, equivalent of a Babinski sign.
Chagas diseasesystemic disease caused by Trypanosoma cruzi
that preferentially affects the myocardium and smooth muscle,
causing dilated cardiomyopathy, megacolon, and achalasia.
Charcot jointdeformed joint caused by repetitive trauma as
a result of diabetic neuropathy, syphilis, leprosy, or syringomyelia.
Charcot-Leyden crystalscolorless needle-shaped crystals
found in sputum of patients with asthma and stools of patients
with ulcerative colitis and amebiasis.
Charcot-Marie-Tooth diseaseperoneal nerve atrophy.
Charcot triad (gastroenterologic)abdominal pain, fever,
and jaundice; indicates ascending cholangitis.
Charcot triad (neurologic)intention tremor, nystagmus,
and scanning speech seen in multiple sclerosis with brainstem
involvement.
Chdiak-Higashi syndromeautosomal recessive neutrophil
and eosinophil disorder characterized by oculocutaneous
albinism, photophobia, nystagmus, and recurrent pyogenic
infections.
Cheyne-Stokes respirationrecurrent pattern of hyperpnea
followed by transient apnea; seen in patients with cerebrovascular and cardiovascular disease.
Chilaiditi syndromeloops of bowel between liver and
diaphragm causing loss of liver dullness; associated with abdominal distension, pain, and vomiting.
Christmas diseasehemophilia B, factor IX deficiency.
Churg-Strauss syndromeallergic granulomatous angiitis;
small-vessel vasculitis of skin, kidneys, and lungs associated
with eosinophilia and asthma.
Chvostek signpercussion of facial nerve in front of the tragus of the ear causes ipsilateral muscular spasm; seen in severe
hypocalcemia.
Cogan syndromenonsyphilitic interstitial keratitis with
vestibuloauditory symptoms; associated with systemic vasculitis and aortic valvulitis.
959
Conn syndromeprimary hyperaldosteronism, hypertension,

and hypokalemic alkalosis.
Cooley anemiathalassemia major.
Corrigan pulsewater-hammer pulse of chronic aortic regurgitation, also seen in hyperdynamic states.
Courvoisier signpainless, hard, palpable gallbladder caused
by ampullary cancer, most commonly carcinoma of the head of
the pancreas.
Cowden diseaseautosomal dominant inheritance with virginal
hypertrophy of breasts, fibrocystic disease, carcinoma of breasts,
bird-like facies, pectus excavatum, and multiple hamartomas of
colon and cerebellum.
Creutzfeldt-Jakob diseaseprogressive degenerative disease
of the central nervous system caused by proteinaceous infectious
particles devoid of nucleic acid (prions); typically presents with
dementia and myoclonus, and usually causes death within 1
year after onset.
Crigler-Najjar syndromehereditary defect in bilirubin
conjugation causing high (type I) to intermediate (type II)
degrees of elevation in serum indirect bilirubin and normal
liver histology.
Crohn diseasegranulomatous enterocolitis.
Cruveilhier-Baumgarten syndromerecanalization of the
umbilical vein secondary to high portal pressures, leading to
caput medusae and a venous bruit over the umbilicus.
Cullen signabdominal wall periumbilical ecchymosis indicative of retroperitoneal hemorrhage; first described with acute
pancreatitis.
Curling ulcergastric ulcer caused by severe systemic stress;
originally associated with large burns.
Cushing diseaseprimary adrenocorticotrophic hypersecretion from pituitary, causing cortical adrenal tumor with hypersecretion of systemic steroids
Cushing phenomenonhypertension and bradycardia indicative of increased intracranial pressure.
Cushing syndromephenotype created by long-term exposure
to endogenous or exogenous corticosteroid excess.
Cushing ulcergastric, duodenal, or esophageal ulcer associated with increased intracranial pressure; presumably due to
gastric acid hypersecretion.
960
V INSIGHTS
D
Darier signstroking of the skin results in edema and erythema in systemic mastocytosis.
De Musset signhead bobbing synchronous with heart beat in
severe chronic aortic insufficiency.
De Quervain tenosynovitixchronic tenosynovitis due to a
narrowing process in the tendon sheaths around abductor pollicis longus and extensor pollicis brevis muscles.
De Quervain thyroiditissubacute nonbacterial thyroiditis.
Devic diseaseneuromyelitis optica, acute attacks of optic
neuritis, and transverse myelitis.
Dieulafoy lesioneroded aberrant gastric submucosal artery
that causes catastrophic upper gastrointestinal tract bleeding.
DiGeorge syndromecardiac abnormality and abnormal
facies, T-cell deficit due to thymic hypoplasia, cleft palate,
hypocalcemia due to hypoparathyroidism resulting from 22q11
deletion (CATCH22 is a helpful mnemonic for this syndrome).
Down syndrometrisomy of chromosome 21.
Dressler syndromeinflammatory pleuropericarditis usually occurring in the second week after myocardial infarction.
Dubin-Johnson syndromeinherited benign disorder of bilirubin metabolism characterized by low-grade direct hyperbilirubinemia and classic black liver due to accumulation of a dark,
granular pigment in the lysosomes of centrilobular hepatocytes.
Duchenne muscular dystrophyX-linked muscular dystrophy
characterized by weakness and hypertrophy of affected muscles.
Duncan syndromealso known as X-linked lymphoproliferative syndrome, a recessive disorder of young boys who die
of fulminant infectious mononucleosis or develop malignant
B-cell lymphomas after infection with Epstein-Barr virus.
Dupuytren contracturecontracture of palmar fascia causing the ring and little fingers to bend into the palm so they cannot be extended.
Duroziez signsystolic and diastolic two-phase murmur that
can be heard over the femoral artery in severe aortic regurgitation
when it is compressed with the bell of the stethoscope.
961
E
Eales diseaseretinal vasculitis with acute sudden loss of vision.
Eaton-Lambert syndromeperipheral motor-sensory
polyneuropathy associated with nonsmall cell lung cancer.
Ebstein anomalycongenital noncyanotic heart disease with
ventricularization of the right atrium secondary to downward displacement of the tricuspid valve from the annulus fibrosus.
Ehlers-Danlos syndromeinherited disorder of collagen characterized by hyperelasticity of the skin, hypermobility of the
joints because of extremely lax ligaments and tendons, and
poor wound healing.
Eisenmenger syndromecyanotic heart defect characterized
by ventricular septal defect, dextroposition of the aorta, pulmonary hypertension with pulmonary artery enlargement, and
hypertrophy of the right ventricle as well as a left-to-right shunt
(ventricular, occasionally also atrial) reverted to right-to-left
by pulmonary hypertension.
Ewart signlocalized area of dullness to percussion, increased
fremitus, and bronchial breathing in lungs of patients with large
pericardial effusions, likely caused by compressive atelectasis.
Ewing tumormalignant sarcoma of shafts of long bones.
Evans syndromehemolytic anemia of warm antibodies and
immune thrombocytopenia.
F
Fabry diseaseX-linked hereditary disorder of -galactosidase A deficiency, characterized by skin telangiectasias in
abdominal and pelvic regions, with paresthesias and exertional fevers.
Fallot tetralogycyanotic heart disease characterized by pulmonic stenosis, ventricular septal defect, dextraposition of the
aorta, and right ventricular hypertrophy.
Fanconi syndromepancytopenia with mental retardation,
absence of a radius, and deformity of long bones; autosomal
recessive disorder.
Felty syndromeatypical form of rheumatoid arthritis with
fever, splenomegaly, and leukopenia and, in some cases, anemia and thrombocytopenia.
Finkelstein testbend thumb into palm and grasp thumb with
962
V INSIGHTS
remaining fingers; pain caused by bending wrist away from
thumb, hyperextending the abductor pollicis longus, indicates a
positive finding and is suggestive of De Quervain tenosynovitis.
Fitz-Hugh-Curtis syndromegonococcal perihepatitis.
Forschheimer spotspetechial enanthema of the soft palate
associated with acute viral syndromes, initially thought to be
pathognomonic for rubella (German measles).
Fournier gangrenenecrotizing fasciitis of the scrotum and
perineal region, usually in diabetics.
Frank signoblique fissure of the ear lobe associated with
coronary artery disease, hypertension, and diabetes mellitus.
Friedreich ataxiaautosomal recessive inherited progressive
degenerative disease with spinal cord atrophy and sclerosis of
the dorsal and lateral columns of the spinal cord that presents
before age 25; characterized by ataxia, dysarthria, and cardiac
manifestations.
G
Gaisbck syndromerelative erythrocytosis due to decreased
plasma volume.
Gallavardin phenomenonmidsystolic murmur of aortic
stenosis becomes more audible, less harsh, and higher pitched
at the apex rather than the base of the heart.
Gardner syndromepolyposis coli associated with soft tissue tumors, bony tumors, and ampullary cancer.
Gaucher diseaseautosomal recessive disorder that results
from defective activity of acid -glucosidase and infiltration
of lipid-laden macrophages (Gaucher cells) in viscera, bones,
and central nervous system; may present as hepatosplenomegaly,
bone disease, or progressive disease of the central nervous system.
Gerstmann syndromecombination of acalculia, dysgraphia,
finger anomia, and right-left disorientation; points to damage
in inferior parietal lobule (angular gyrus) of the left cerebral
hemisphere.
Gibson murmurcontinuous machinery murmur of patent
ductus arteriosus; best heard over the left second intercostal
space.
963
Gilbert syndromehereditary defect of bilirubin metabolism

that causes mild, benign increase in indirect bilirubinemia.
Gilles de la Tourette syndromeautosomal dominant hereditary disorder characterized by motor and phonic tics, with
coprolalia, echolalia, and palinphrasia.
Gitelman syndromeinherited autosomal recessive mineralocorticoid deficiency syndrome characterized by renal salt wasting,
activation of the renin-aldosterone system, with low blood pressure, low serum levels of potassium and magnesium, high serum
levels of bicarbonate, and decreased urinary calcium excretion.
Glanzmann thrombastheniaautosomal recessive disorder
due to deficiency of the glycoprotein IIb-IIIa complex, thus
unable to bind fibrinogen; characterized by normal-sized
platelets that adhere but do not aggregate, causing impaired
hemostasis and severe spontaneous mucosal bleeding.
Gohn focuscalcified nodule seen on chest X-ray; due to
healed primary TB.
Goodpasture syndromeantiglomerular basement membrane
nephritis with lung hemorrhage.
Gottron signerythema of the knuckles, with a raised, violaceous, scaly eruption characteristic of dermatomyositis.
Gowers signpatients with muscular dystrophy use arms to
push themselves erect by moving their hands up their thighs
to compensate for weakness of leg and hip flexors.
Graham Steell murmurhigh-pitched, diastolic, decrescendo, blowing murmur of pulmonary regurgitation heard along the
left sternal border; result of dilatation of the pulmonic valve
ring from severe pulmonary hypertension.
Graves diseasethyrotoxicosis caused by thyroid-stimulating immunoglobulins directed against thyroid-stimulating hormone receptor, resulting in the classic clinical state of hyperthyroidism with goiter, ophthalmopathy, and dermopathy.
Guillain-Barr syndromerapidly evolving, ascending,
autoimmune, symmetric areflexic motor paralysis with or without sensory involvement.
H
Hageman factorfactor XII.
Hallervorden-Spatz diseaseneurodegeneration with brain
iron accumulation type 1; is either sporadic or autosomal reces964
V INSIGHTS
sive progressive disease, with onset in late childhood; characterized by extrapyramidal signs, spasticity, dystonia, dysarthria
with dementia, and emotional disturbances.
Hamman-Rich syndromemore commonly known as acute
interstitial pneumonia, a fulminant type of interstitial lung
disease characterized by diffuse, bilateral airspace opacification
on chest X-ray and diffuse alveolar damage on lung biopsy.
Hamman signauscultatory crunching sound synchronous
with the heartbeat; heard in pneumomediastinum.
Hampton humpradiographic wedge-shaped density above
the diaphragm seen in pulmonary embolism and thought to
reflect a peripheral area of lung infarction.
Ham testoutdated laboratory demonstration of lysis of RBCs
after complement activation by acid; diagnostic of paroxysmal
nocturnal hemoglobinuria.
Hand-Schller-Christian diseasediabetes insipidus, exophthalmos, and punched-out bone lesions; caused by histiocytosis X.
Hansen diseaseleprosy.
Hashimoto thyroiditisautoimmune lymphocytic infiltration of the thyroid gland causing hypothyroidism.
Heberden nodeshard nodules that develop around the distal interphalangeal joints; pathognomonic of osteoarthritis.
Heefordt syndromeone of two acute sarcoidosis syndromes;
characterized by fever, parotid enlargement, anterior uveitis,
and facial nerve palsy.
Hecht pneumoniaprimary giant cell pneumonia in rubeola.
Heinz bodiessmall deep purple granular inclusions in RBCs
of patients with certain hemolytic anemias, especially thalassemia.
Henoch-Schnlein purpurasmall-vessel vasculitis characterized by palpable purpura in buttocks and thighs, abdominal
pain, arthralgias, and IgA glomerulonephritis.
Heimlich maneuversudden and forceful application of subdiaphragmatic pressure to the chest in an attempt to expel a
foreign body from the trachea or pharynx, where it is causing
danger of suffocation.
Hill signblood pressure in the arm >30 mm Hg when compared
with blood pressure in the leg; seen in severe aortic regurgitation.
965
Hodgkin diseasemalignant lymphoma characterized by diffuse, symmetric lymphadenopathy.

Hoffmann signthumb flexion caused by flicking the nail of
either the second, third, or, fourth finger, in hyperreflexia states,
including upper motor neuron disease.
Hollenhorst plaquecholesterol embolus seen in branching
of retinal arterioles of patients with amaurosis fugax.
Holt-Oram syndromeautosomal dominant disorder with
upper limb dysplasia, atrial septal defects, and conduction disturbances in the atrioventricular node.
Homan signcalf pain caused by dorsiflexion of the foot in
patients with deep venous thrombosis of the lower extremities.
Hoover signinspiratory retraction of lower rib margins in
patients with COPD.
Horner syndromeunilateral ptosis, miosis, and anhidrosis;
can be associated with lung cancer impinging on the sympathetic
chain, carotid dissection, or brainstem stroke.
Howell-Jolly bodiesglobular nuclear fragments in RBCs of
patients who have been splenectomized or have megaloblastic
anemia.
Hunner ulcerchronic vesical ulcer at the vertex of the bladder suggestive of interstitial cystitis.
Huntington diseaseinherited autosomal dominant degenerative brain disorder characterized by chorea and behavioral
abnormalities.
Hurler syndromeautosomal recessive mucopolysaccharidosis, resulting from alpha-L-iduronidase deficiency; characterized by coarse (gargoyle) facial features, hunchback, mental retardation, hepatosplenomegaly, and cardiac defects.
Hutchinson triadcranial nerve VIII deafness, notched teeth,
and interstitial keratitis; seen in congenital syphilis.
J
Jaccoud arthritisprogressive, deforming arthropathy of
hands and feet of young patients with recurrent rheumatic fever
or systemic lupus erythematosus.
Jacksonian seizureseizure activity that starts in a localized
part of the body, such as the hand or arm, and spreads, becoming generalized; indicative of a focal lesion in the contralateral motor cortex.
966
V INSIGHTS
Jacod triadoptic atrophy, total ophthalmoplegia, and trigeminal neuralgia usually due to nasopharyngeal tumor.
Janeway lesiona painless hemorrhagic macule on the palms or
soles thought to be a vasculitic process in infectious endocarditis.
Jarisch-Herxheimer reactiongeneralized rash, fever, and
malaise during the first days of antibiotic treatment of leptospirosis, Lyme disease, or syphilis.
Jatene operationoperation to correct transposition of the
great vessels.
Jendrassik maneuverused to facilitate testing of the knee
jerk by asking patients to hook their fingers together and then
pull strongly in abduction.
Jod-Basedow phenomenonhyperthyroidism induced by
exogenous iodine.
K
Kaposi sarcomamulticentric neoplasm consisting of multiple vascular nodules and strongly associated with human herpesvirus type 8 (HHV-8); occurs in skin, mucous membranes, and
viscera and is seen most frequently in patients with AIDS.
Karnofsky performance scalean index of clinical estimate
of a patients physical state, performance, and prognosis to help
evaluate his or her suitability for a therapeutic procedure; most
commonly used in oncology before chemotherapy and surgery.
Kartagener syndromesubgroup of immotile cilia syndrome,
autosomal recessive; characterized by situs inversus, chronic
sinusitis, and bronchiectasis.
Kasabach-Merritt syndromeextensive and progressively
enlarging vascular malformation that causes stagnant blood
flow and disseminated intravascular coagulation, with thrombocytopenia and purpura.
Kawasaki diseasemucocutaneous lymph node syndrome;
acute febrile multisystem disease of children that may be associated to coronary aneurysms in 25% of patients and may cause
acute myocardial infarction in children.
Kayser-Fleischer ringgray-green or brownish pigmented
ring, 1-3 mm broad, in the deep epithelial layers at the outer
967
border of the cornea and pathogonomic for copper deposition

in Wilson disease.
Kearns-Sayre syndromesporadic noninherited mitochondrial
DNA disorder characterized by the triad of progressive external ophthalmoplegia, pigmentary degeneration of the retina,
and heart block.
Kehr signradiated pain and hyperesthesia of the left shoulder in splenic rupture or subdiaphragmatic abscess.
Kernig signan attempt to extend the knee when the thighs are
flexed over the hips causes pain in patients with meningeal irritation.
Kikuchi diseasebenign cervical necrotizing lymphadenitis
in young women.
Kimmelstiel-Wilson lesionnodular diabetic glomerulosclerosis.
Klatskin tumorbile duct carcinoma localized at the bifurcation of the hepatic ducts.
Klinefelter syndromeXXY syndrome with hypogonadism,
hypogenitalism, and mental retardation.
Klippel-Trnaunay syndromesporadic syndrome with vascular malformation of the limbs, gross limb hypertrophy, and
arteriovenous fistulas.
Klver-Bucy syndromebilateral lesions of the amygdala
and temporal cortex produce visual agnosia, hyperphagia, emotional apathy, and hypersexual behavior.
Koebner phenomenonalso called isomorphic response,
refers to formation of skin lesions along a site of injury; seen
with lichen planus, psoriasis, and systemic juvenile rheumatoid arthritis.
Koplik spotsbright red spots on the inside of the cheek and
pathognomonic for rubeola.
Korotkoff soundspulse-synchronous circulatory sounds
heard through the stethoscope in auscultation of blood pressure using a sphygmomanometer when pressure over the artery
is reduced below systolic arterial pressure.
Krukenberg tumorgastric carcinoma metastases to the
ovary, usually bilateral.
Kussmaul respirationrhythmic, gasping, and very deep
type of respiration with normal or reduced frequency; associated with severe diabetic or renal acidosis or coma.
Kussmaul signjugular venous pulse increases with deep inspiration (when it normally would decrease because of increased
968
V INSIGHTS
venous return to the right atrium), indicating limited expansion
of the right ventricle, as found in restrictive pericarditis.
Kveim-Stilzbach testformation of a granuloma after injection of Kveim antigen in patients with sarcoidosis.
L
Lannec cirrhosismacronodular cirrhosis caused by alcohol
consumption.
Lasgue signswhen a patient is supine with the hip flexed, dorsiflexion of the ankle causes pain or muscle spasm in the posterior thigh and back; seen in irritation of lumbar root or sciatic nerve.
Legg-Calv-Perthes diseaseautosomal dominant disorder
causing unilateral or bilateral aseptic vascular necrosis of the
femoral head.
Lemierre syndromesuppurative thrombophlebitis of the
internal jugular vein with sepsis and septic metastasis to the
lung, brain, and kidneys, usually caused by fusobacteria.
Lengre diseaseprimary sclerodegenerative disease of the
conducting system of the heart causing heart block with no
other cardiac abnormalities.
Leriche syndromeatheromatous involvement or occlusion
of the abdominal aorta just above its bifurcation, causing inability to maintain penile erection, fatigue in the lower limbs,
cramps in the calf area, ischemic pain of intermittent bilateral
gluteal claudication, absent or diminished femoral pulse, pallor, and coldness of the feet and legs.
Lesch-Nyhan syndromeX-linked complete deficiency of
hypoxanthine phosphoribosyltransferase causing hyperuricemia,
self-mutilating behavior, choreoathetosis, spasticity, and mental retardation.
Lev diseasecalcification of the fibrous cardiac skeleton,
which frequently involves the aortic and mitral valves, the
fibrous skeleton, and the apical ventricular septum, causing
atrioventricular and bundle branch block.
Levine signa gesture of clenching the fist over the sternum
used by patients when describing anginal chest pain; it is highly specific for a coronary origin of the pain.
969
Lewy body diseasedementia caused by diffuse cortical infiltration of Lewy bodies (intraneuronal cytoplasmic inclusions).
Lhermitte signsensation of an electric shock down the spine
caused by neck flexion or coughing in patients with multiple
sclerosis or other spinal cord disease.
Libman-Sacks endocarditisnoninfectious thrombotic endocarditis in patients with systemic lupus erythematosus or malignancies.
Lffler endocarditisendocardial and myocardial infiltration by eosinophils in hypereosinophilic syndrome, with formation of large ventricular mural thrombi.
Lffler syndromebenign acute eosinophilic syndrome characterized by migrating pulmonary infiltrates and mild clinical
symptoms.
Lfgren syndromeone of two acute sarcoidosis syndromes
characterized by erythema nodosum with bilateral hilar adenopathy seen on chest X-ray and polyarthritis.
Lou Gehrig diseaseamyotrophic lateral sclerosis.
Ludwig anginaPeriodontal infection, usually arising around
the third molar, which causes submandibular cellulitis, trismus, and neck swelling with respiratory distress.
Lutembacher syndromecongenital or acquired heart disease in which atrial septal defect is combined with mitral
stenosis.
Lyme diseaseinfectious tick-borne disease caused by Borrelia
burgdorferi, begins with a characteristic skin rash (erythema
migrans) but may become systemic.
Lynch syndromehereditary nonpolyposis colon cancer.
M
MacCallum patchvegetations found along the mural surface of a cardiac chamber.
Machado-Guerreiro testa complement-fixation test for
Trypanosoma cruzi infection (Chagas disease).
Machado-Joseph diseasespinocerebellar ataxia type 3;
rare, progressive hereditary ataxia initially described in
Portuguese descendants; features are similar to those of
Parkinson disease.
Mallory-Weiss tearsvertical tears in the esophagus caused
by severe repetitive vomiting.
970
V INSIGHTS
Marfan syndromeAutosomal dominant hereditary disorder of
connective tissue affecting primarily the musculoskeletal system,
cardiovascular system, and eye; characterized by tall stature, long
extremities, arachnodactyly, arm span greater than height, poorly
developed musculature, laxity of the joints and ligaments, thoracic cage abnormalities, kyphosis, dorsal scoliosis, flat feet, hammer toes, dislocation of the lens, aortic insufficiency, and ascending aortic aneurysms (not all these features need to be present).
Means-Lerman scratchscratchy systolic ejection murmur
due to hyperthyroidism.
Meckel diverticulumdiverticulum of the ileum, a vestige of the
yolk stalk, about 6-10 cm long, shaped like a gloves finger, found
approximately 2 ft from the ileocecal valve.
Mees lineswhite transverse lines in fingernails associated
with chronic arsenic intoxication.
Meige syndromechronic familial lymphedema of the limbs,
which manifests with pittings and brawny edema of the ankles
and shins; often associated with inflammation and various
defects, including distichiasis, extradural cysts, vertebral anomalies, cerebrovascular malformations, yellow nails, and sensorineural hearing loss.
Meigs syndromecharacterized by a solid ovarian tumor,
usually a fibroma, accompanied by ascites and hydrothorax.
Meleney ulcergradually expanding ulcer developing at the
site of trauma or surgery; caused by synergistic infection, including anaerobic streptococci.
Mendelson syndromechemical aspiration pneumonitis
caused by regurgitation and aspiration of gastric contents.
Mntrier diseasecaused by large tortuous gastric mucosal
folds resulting in epigastric pain and protein-losing gastropathy.
Meniere diseaseprogressive sensorineural hearing loss and
vertigo; frequently accompanied by nausea and vomiting, ringing in the ears, a sensation of fullness or pressure in the ears, and
sometimes nystagmus.
Milroy diseasecongenital lymphedema, same as Meige disease.
Mitsuda reactiona local immune response to SQ injection
of Mycobacterium leprae used to measure delayed-type hypersensitivity to the pathogen.
971
Mondor diseaserare entity characterized by sclerosing thrombophlebitis of the veins in the anterior chest wall, usually a
result of direct trauma.
Morton neuromaa painful, benign fibroinflammatory tumor
developing around the plantar digital nerve, most commonly
between the third and fourth interdigital spaces, caused by
entrapment neuropathy, most often in women.
Moyamoya diseaseocclusive disease involving large intracranial arteries with development of rich collateral circulation,
which is prone to bleeding, around the occluded artery, producing the diagnostic arteriographic appearance of puff of
smoke (Japanese moyamoya).
Mller signsystolic pulsations of the uvula in aortic
insufficiency.
Munchausen syndromesomatiform disorder characterized
by severe, chronic, dramatic factitious illness, particularly
seizures, asthma, hematuria, or chronic diarrhea.
Murphy signinterrupted inspiration by palpation of a tender,
enlarged gallbladder in acute cholecystitis.
N
Negri bodiespathognomonic cytoplasmic inclusions in neurons of patients with rabies.
Nelson syndromehyperpigmentation and high ACTH levels
despite adequate corticosteroid replacement, caused by residual pituitary tumor after bilateral adrenalectomy in patients
with pituitary Cushing disease.
Nikolsky signseparation of epidermis of patients with pemphigus vulgaris by manual compression of the skin.
Niemann-Pick diseaseinherited autosomal recessive lysosomal storage disorder of early infancy characterized by failure
to thrive, hepatosplenomegaly, and rapidly progressive neurodegeneration.
Noonan syndromea complex multisystem syndrome similar to Turner syndrome but can occur in both sexes and has no
karyotype abnormality; features include unusual facies (i.e.,
hypertelorism, down-slanting eyes), webbed neck, congenital
heart disease, short stature, chest deformity, and mental
retardation.
972
V INSIGHTS
O
Ogilvie syndromeacute metabolic colonic pseudo-obstruction.
Oliver-Cardarelli signpulsation of the larynx synchronous
with ventricular systole; elicited when the larynx is grasped
between the thumb and index finger while the patient is in the
erect position. It is indicative of an aneurysm of the aortic
arch, mediastinal tumors, and COPD.
Ondine curseobserved in primary alveolar hypoventilation,
in which patients have frequent episodes of central apnea when
asleep.
Oppenheim reflex(a Babinski equivalent) firm stroke or other
irritation along the medial side of the tibia causes dorsiflexion of
the great toe of patients with upper motor neuron disease.
Ortner syndromehoarseness caused by compression of
recurrent laryngeal nerve by enlarged left atrium in patients
with mitral stenosis.
Osborne wavean electrocardiographic wave that distorts the
QRS-ST junction in patients with hypothermia.
Osgood-Schlatter diseaseosteochondrosis of the tibial
tuberosity.
Osler maneuvereasily palpable and rigid radial artery despite
obliteration of the radial pulse by a sphygmomanometer; indicating unreliability (and likely overestimation) of cuff measurement of blood pressure because of severe arteriosclerosis
of the artery.
Osler nodessmall, erythematous, exquisitely painful nodes
at the tips of fingers and toes; thought to be embolic phenomena from infective endocarditis.
Osler-Weber-Rendu syndromehereditary telangiectasia
syndrome.
P
Page kidneyrenal subcapsular hematoma that causes
parenchymal compression with secondary hypertension.
973
Paget diseaseosteitis deformans, caused by generalized

excessive resorption of bone by osteoclasts; causes bone pain,
bone deformity, and widespread intraosseous fistulas that may
result in high-output heart failure.
Palla signradiologic enlargement of the right descending
pulmonary artery seen in pulmonary embolism.
Pancoast syndromeusually a squamous cell carcinoma at the
apex of the lungs compresses the sympathetic plexus and erodes
into the rib cage, causing back and arm pain and Horner
syndrome.
Parinaud syndromedorsal midbrain syndrome characterized by supranuclear palsy of vertical conjugate movement,
most often upwards, and caused by lesions near the aqueduct
of Sylvius
Parkinson diseaseprogressive degenerative central nervous
system disease characterized by destruction of neurons in the
pigmented substantia nigra (pars compacta), locus ceruleus,
globus pallidus, and putamen, resulting in loss of dopaminergic cells and depletion of striatal dopamine; clinically
characterized by rest tremor, rigidity, bradykinesia, and gait
instability.
Pastia linespetechiae in body folds of patients with scarlet
fever.
Paterson-Kelly syndromeesophageal web in association
with glossitis and iron deficiency anemia. (Better known as
Plummer-Vinson syndrome.)
Pel-Ebstein feverfever that persists for days to weeks, disappears and then recurs; seen in Hodgkin disease.
Pemberton signface plethora and syncope caused by compression of neck vasculature by large retrosternal goiter.
Peutz-Jeghers syndromeautosomal dominant inherited
disorder characterized by intestinal hamartomatous polyps
in association with mucocutaneous melanocytic macules;
has a high predisposition to cancer of the gastrointestinal
tract.
Peyronie diseaseinduration of the corpora cavernosa of the
penis, causing distortion and pronounced curvature of the penis,
with erectile dysfunction.
Phalen testparesthesia in the median nerve distribution by
pressing the extensor surfaces of the two flexed wrists against
each other, in carpal tunnel syndrome.
974
V INSIGHTS
Pick diseaseslowly progressive neurodegenerative disorder
similar to Alzheimer disease; diagnosis requires autopsy confirmation with the pathologic finding of Pick bodies.
Pickwickian syndromeobesity-hypoventilation syndrome,
with daytime hypersomnolence, hypercapnea, polycythemia,
pulmonary hypertension, and right-sided heart failure.
Plummer nailsseparation of the nail from the nailbed (onycholysis) in Graves disease
Plummer-Vinson syndromesame as Paterson-Kelly syndrome.
Pott diseasetuberculous osteomyelitis of the spine.
Prinzmetal anginavasospastic angina.
Purtscher retinopathyhemorrhagic and vaso-occlusive vasculopathy characterized by multiple white retinal patches and
retinal hemorrhages with acute blindness; associated with severe
head and chest trauma and acute pancreatitis.
Q
Quincke signsystolic plethora and diastolic blanching in the nail
bed with slight compression; observed in aortic insufficiency.
R
Ramsay Hunt syndromevaricella-zoster virus infection
involving the geniculate ganglion of the sensory branch of cranial nerve VII (facial nerve) and resulting in pain and vesicles
in the auditory canal, loss of taste sensation in the anterior twothirds of the tongue, and ipsilateral facial palsy.
Rasmussen aneurysmdilated vessel that ruptures into a
tuberculous pulmonary cavity and causes hemoptysis.
Raynaud diseaseoccurrence of Raynaud phenomenon in
the absence of its known secondary causes.
Raynaud phenomenonepisodic digital ischemia manifested by sequential blanching, cyanosis, and rubor of the fingers
following cold exposure.
Reed-Sternberg cellgiant connective tissue cells with one or
two large nuclei (mirror image nuclei) characteristic of the
lesions of Hodgkin disease.
975
Reiter syndromenongonococcal urethritis, uveitis, and reactive arthritis.

Reye syndromeacute childhood illness associated with the
combination of viral illness and drugs (especially salicylates),
causing cerebral edema and renal and hepatic insufficiency.
Reynolds pentadfever, abdominal pain, jaundice, hypotension, and confusion in septic acute cholangitis.
Richter syndrometransformation of chronic lymphocytic
leukemia or small lymphocytic lymphoma into aggressive diffuse large B-cell lymphoma.
Riedel thyroiditischronic fibrosing, painless thyroiditis.
Riley-Day syndromefamilial dysautonomia.
Ritter diseasestaphylococcal toxic epidermal necrolysis in
newborns.
Romaa signunilateral painless edema of the palpebrae in
acute Chagas disease.
Romberg signthe patient cannot maintain body balance when
standing with feet together and eyes closed; the sign is present if
the patient sways and falls when the eyes are closed; falling is
often to the same side and indicates posterior column disease.
Roth spotsretinal red spots with white center seen in infective endocarditis and some leukemias.
Rovsing signpressure over the descending colon causes pain
in the right lower quadrant of the abdomen of patients with
acute appendicitis.
S
Saint Vitus danceSydenham chorea of rheumatoid fever.
Schatzki ringa thin weblike constriction at the squamocolumnar junction or near the border of the lower esophageal
sphincter.
Schmidt syndromeautoimmune polyglandular failure.
Schober testtest that measures flexion of the lumbar spine in
patients with ankylosing spondylitis who have impaired flexion.
Szary syndromecutaneous T-cell lymphoma (mycosis fungoides) with peripheral blood involvement.
Sheehan syndromepostpartum pituitary infarction in the
setting of hemorrhage and systemic hypotension.
Shy-Drager syndromea form of multiple system atrophy characterized by autonomic dysfunction and parkinsonian features.
976
V INSIGHTS
Sipple syndromemultiple endocrine neoplasia type IIA;
characterized by medullary thyroid carcinoma, hyperparathyroidism, and pheochromocytoma.
Sister Mary Joseph noduleperiumbilical metastases from
gastrointestinal tract malignancies.
Sjgren syndromechronic autoimmune lymphocytic infiltration of exocrine glands causing xerostomia, dry eyes, and
systemic manifestations.
Somogyi phenomenonrebound hyperglycemia after an
episode of hypoglycemia.
Starling lawthe force of contraction of the cardiac muscle is
proportional to its initial length.
Stauffer syndromeparaneoplastic nonmetastatic liver dysfunction in patients with renal cell carcinoma.
Stevens-Johnson syndromedrug-induced severe erythema
multiforme-like eruption of the skin, lesions of the oral, genital, and anal mucosae, and hemorrhagic crusting on the lips;
associated with fever, headache, and arthralgia.
Still diseaseadult juvenile rheumatoid arthritis.
Stokes-Adams syndromeintermittent high-degree atrioventricular block with syncope.
Strachan syndromealso known as Jamaican neuritis and
characterized by amblyopia, optic neuritis, painful peripheral
neuropathy, and orogenital dermatitis; occurs in undernourished populations of tropical countries.
Sturge-Weber syndromeneurocutaneous syndrome characterized by unilateral facial port-wine nevus, cerebral atrophy, and oculomeningeal capillary hemangiomata.
Sydenham choreachorea associated with acute rheumatic
fever.
Symmers fibrosisperiportal liver fibrosis associated with
schistosomiasis.
Sweet syndromeacute febrile neutrophilic dermatosis characterized by sudden onset of fever, leukocytosis, and tender,
erythematous, well-demarcated papules and plaques showing
dense neutrophilic infiltrates on histologic examination.
Although Sweet syndrome may occur in the absence of other
known disease, it is often associated with hematologic disease
977
(including leukemia) and immunologic disease (rheumatoid

arthritis, inflammatory bowel disease).
T
Takayasu arteritisinflammatory and stenotic disease of
medium- and large-sized arteries, especially the aortic arch and
its branches.
Tako-tsubo syndrometransient ballooning of the cardiac
apex associated with severe acute illness in the absence of coronary disease.
Tietze syndromepainful, swollen, and red costochondrial joint.
Tinel signparesthesia in the distribution of median nerve
produced by tapping the volar aspect of the wrist.
Todd paralysistransient limb paralysis after generalized
seizures.
Tolosa-Hunt syndromerecurrent, sharp unilateral retroorbital pain with extraocular palsies, usually involving cranial
nerves III, IV, V, and VI; other features include proptosis and sensory loss over the forehead, sluggish pupil reaction to light,
and diminished corneal sensitivity with blurred vision up to
complete blindness.
Troisier signmetastatic enlargement of left supraclavicular
lymph nodes from an obscurely located primary cancer, usually
in the gastrointestinal tract or lungs.
Trousseau syndromeparaneoplastic migratory thrombophlebitis; usually associated with pancreatic cancer.
Turcot syndromepolyposis coli associated with malignant
tumors of the central nervous system.
Turner signblue-purple discoloration of the costovertebral
angles that occurs in hemoperitoneum caused by acute pancreatitis.
Turner syndromegonadal dysgenesis in women caused by
genetic defects of the X chromosome; characterized by primary amenorrhea, sexual infantilism, short stature, and multiple congenital defects.
V
Valsalva maneuverthe patient maintains a constant expiratory pressure for at least 15 seconds while changes in blood
pressure and heart rate are observed.
978
V INSIGHTS
Verner-Morrison syndromewatery diarrhea, hypokalemia,
and renal failure in association with pancreatic islet cell tumors
(VIPomas) that secrete large quantities of vasoactive intestinal peptide (VIP).
Vincent anginaacute necrotizing ulcerative gingivitis caused
by Treponema vincentii and Fusobacterium nucleatum.
Virchow nodesupraclavicular adenopathy associated with
malignancy of the gastrointestinal tract.
Virchow triadthree functional causes of thrombosis: epithelial changes, changes in blood flow, and changes in blood
viscosity.
Vogt-Koyanagi-Harada syndromeuveomeningeal syndrome characterized by anterior uveitis associated with poliosis, vitiligo, auditory disturbances, and meningeal irritation.
von Hippel-Lindau syndromeassociation of central nervous system tumor, renal cell carcinoma, pheochromocytoma, and
islet cell neoplasm.
von Recklinghausen diseaseneurofibromatosis type I, multiple skin neurofibromas, caf au lait spots, and pheochromocytomas.
von Willebrand diseaseautosomal dominant disease characterized by bleeding disorder resulting from deficiency of von
Willebrand factor.
W
Waldenstrm macroglobulinemiahematologic malignancy of lymphoplasmacytoid cells that secrete IgM; similar to
multiple myeloma except it has a more benign course.
Wallenberg syndromeocclusion of the posterior inferior
cerebellar artery supplying the dorsolateral medulla and posteroinferior cerebellum results in pain and impaired sensation
in the ipsilateral half of the face, ataxia of limbs and falling
toward the side of the lesion, nystagmus, diplopia, Horner syndrome, dysphagia, hoarseness, and impaired pain and temperature on contralateral side of the body.
Waterhouse-Friderichsen syndromebilateral hemorrhagic necrosis of the adrenal glands in severe meningococcal disease.
979
Wegener granulomatosisan antineutrophil cytoplasmic antibody (ANCA)-associated systemic necrotizing granulomatous

vasculitis of small arteries and veins of the upper and lower
respiratory tracts, kidneys, and other organ systems.
Weil syndromehemorrhagic form of leptospirosis causing
acute renal failure, shock, and disseminated intravascular coagulation.
Wermer syndromemultiple endocrine neoplasia type I,
characterized by neoplasia of the parathyroid, pituitary, and
pancreatic islet cells.
Werner syndromeadult progeria; hereditary multisystem
disorder characterized by premature aging, dwarfism, premature graying of the hair (canities), alopecia, scleroderma-like skin
changes, trophic leg ulcers, cataracts, hypogonadism, diabetes
mellitus, calcification of blood vessels, and osteoporosis.
Wernicke aphasiainability to comprehend written and spoken language.
Wernicke encephalopathymetabolic encephalopathy caused
by thiamine deficiency, usually in the setting of alcoholism,
and characterized by the clinical triad of ophthalmoplegia, ataxia, and global confusion.
Westermark signfocal oligemia on chest X-ray in pulmonary
embolism.
Whipple diseasesystemic indolent infection caused by
Tropheryma whippelii and manifested by arthralgia, abdominal
pain, chronic diarrhea, progressive weight loss, low-grade fever,
skin hyperpigmentation, and peripheral lymphadenopathy.
Whipple triadsymptoms of hypoglycemia, documentation
of hypoglycemia, and relief of symptoms with administration
of glucose; originally described in association with insulinomas.
Williams syndromeidiopathic hypercalcemia of infancy;
characterized by elfin facies, mental retardation, and supravalvular aortic stenosis in association with hypercalcemia secondary
to increased sensitivity to vitamin D.
Wilms tumorthe most common renal tumor in children; it
arises from the primitive embryonal renal tissue and contains
epithelial, stromal, and blastemal elements; it presents as an
abdominal mass and has a 90% rate of cure.
Wilson diseaseautosomal recessive defect of biliary copper
excretion that may lead to liver disease and neuropsychiatric
manifestations.
980
V INSIGHTS
Wiskott-Aldrich syndromeX-linked recessive disorder with
a defect in both T- and B-cell function and characterized by
the triad of eczema, profound thrombocytopenia, and frequent
infections.
Wolff-Parkinson-White syndromecardiac preexcitation
syndrome in which atrioventricular conduction may occur
through an accessory pathway, most commonly the bundle of
Kent; it is characterized by episodes of supraventricular tachycardia, short PR interval, and the presence of a delta wave on
the ECG.
Y
Young syndrometriad of bronchiectasis, obstructive
azoospermia with reduced fertility, and chronic rhinosinusitis
infections.
Z
Zenker diverticulumoutpouching of the esophageal wall
in the posterior hypopharyngeal wall.
Zollinger-Ellison syndromeexcessive gastrin production
by a gastrinoma, clinically manifested by numerous gastrointestinal ulcers and recurrent gastrointestinal tract bleeding.
981
V INSIGHTS
EVIDENCE-BASED PRACTICE
Victor M. Montori, M.D., M.Sc.
PROBLEM
The interview and examination represent the first diagnostic
test.
How do you select lab tests?
What treatments do you start?
How do you explain the risks and benefits of your diagnostic and therapeutic strategies to the patient, the one who takes
those risks and suffers the harms and benefits?
GENERAL APPROACH
Patient-Centered Approach
The patients best interest is the only interest to be considered.
Evidence-Based
Do not be evidence-centeredresearch reports alone never
tell you what to do.
Do not ignore evidencepatients suffered to produce it.
Do not ignore the advice of local experts, but be critical.
Do not believe all you read, be very critical.
Explicit and Mindful

If you make a decision, know why you are making it and be
ready to defend it.
In all decisions, be aware of the patients preferences and
valuesonly the patient knows these and they could be different from yours.
Be aware of the limits set by the care environment on the
options you can consider.
Be aware of the reactions and emotions you experience and
explore themthey influence your judgment.
983
How to Make a Problem Familiar

Read. Acquire knowledge. Know patterns. See patients.
Recognize patterns. Problems become familiar with experience. Be ready to learn from every patient.
How to Structure Solutions to Problems
Analyze the Problem
For each case, determine the differential diagnosis.
To determine your approach, stratify the differential diagnosis according to the following (Table 1):
Plan your diagnostic strategy; know the test characteristics.
Choose a sensitive test to rule out disease.
Choose a specific test to rule in disease.
Formulate the Clinical Question
Fill in the following blanks:
Your patient:_________________
Test: _______________________
Reference standard: ___________
Diagnosis:___________________
Search for evidence to formulate a diagnostic strategy.
Critically appraise the data.
Was the study prospective, with a spectrum of patients
similar to those in whom the test will be applied (was
there diagnostic uncertainty)?
Were the assessment of the reference standard and the test
independent and blind to each other? Did everyone receive
the same reference standard?
Results
Look for sensitivity, specificity, or likelihood ratios.
The likelihood ratio is the proportion of people with disease
and the test result divided by the proportion of people without disease and the test result (Fig. 1).
Calculation of posttest probability is shown in Figure 2.
Plan the Therapeutic Strategy

Know the risks and benefits of treating. Value observation
(over the need to act).
Treatment goals need to be negotiated with the patient.
Monitor the treatment.
984
V INSIGHTS
Table 1. Diagnostic Strategy
Strategy
Reason
Example
Treat probable
disease
Disease probability
is high and/or disease
is severe
Treatment can be
started without test
results
Disease probability is
intermediate
Wait for test results to
start treatment
low but risk of late/
missed diagnosis is
not acceptable
Sublingual nitroglycerin & aspirin for a

smoker with coronary
artery disease who has
chest pain
Diagnostic tests
Rule out
Keep in mind
extremely low or
Risk of late/missed
diagnosis is acceptable
Ferritin level in a
middle-aged man with
anemia to diagnose
iron-deficiency anemia
Serial ECG and cardiac
enzymes in patient
with atypical chest
pain to rule out myocardial infarction
Metanephrines in urine
to diagnose pheochromocytoma in
patient with recurrent
headaches
What are the measures to judge effectiveness, harm, side

effects?
Validity Criteria
Was the assignment to treatment randomized?
Was the allocation concealed? (Were the persons who decided about participant inclusion separated from those who allocated patients to the experimental arms?)
Were the groups similar at the beginning of the trial? Were
all subjects followed to its completion?
Were all groups (patients, healthcare providers, data collectors, data analysts, judicial assessors of outcomes, authors)
in the study blinded?
Were patients analyzed in the groups to which they were
randomly assigned (intention to treat)?
985
986
LR+
=
(of a positive test)
LR
=
(of a negative test)
Fig. 1. Likelihood ratio (LR).
+ test/disease
sensitivity
=
+ test/no disease
1-specificity
test/disease
1-sensitivity
=
test/no disease
specificity
V INSIGHTS
0.1
99
0.2
0.5
1,000
1
2
5
10
20
30
40
50
60
70
80
90
95
500
200
100
50
20
10
5
2
1
0.5
0.2
0.05
0.02
0.01
0.005
0.002
0.001
95
90
80
70
60
50
40
30
20
10
5
2
1
0.5
0.2
99
0.1
Fig. 2. Plug in the pretest probability of the disease (prevalence of the

disease in your practice setting, your best guess). Next, use a straight
angle through the likelihood ratio to calculate the posttest probability.
(From Fagan TJ. Nomogram for Bayess theorem [letter]. N Engl J
Med. 1975;293:257. Used with permission)
987
Results
Look for the risks of both groups.
The risk difference is the absolute risk reduction.
The inverse is the number needed-to-treat.
Look for the risks of harm in both groups.
Follow the same steps, and calculate the number neededto-harm.
It is easier to trust a body of literature (or a systematic review
of several trials) than a single trial.
The evidence alone does not tell you what to do.
Lack of evidence of effectiveness does not mean lack of
effectiveness.
Before you use these results, ask if your patient and setting is
so different from the average patient and setting in the study that
the results are likely to be different in your patient and setting.
Once you are familiar with the evidence and with your
patients preferences and values, try to identify the following:
What are the limits imposed by my reality on the range of
options I am considering?
What are the local standards for the treatment and diagnostic options considered?
After this extensive evaluation, you are more likely to feel
comfortable with the diagnostic and therapeutic answers to
your patient problem.
With more experience, you will be able to recognize this
problem, be familiar with it, and have a structured answer to
apply to its solution.
EVIDENCE SOURCES
The ACP Journal Club: www.acpjc.org
Summaries of important research of high methodologic
validity. Valuable for remaining updated.
The Cochrane Collaboration (systematic reviews of therapy
trials): www.cochranelibrary.com
High-quality systematic review of therapeutic trials.
MEDLINE: www.pubmed.gov
Massive database of biomedical research.
988
V INSIGHTS
HOW TO BE A GOOD INTERN
Jason Persoff, M.D.
GENERAL ADVICE
All interns feel overwhelmed by the awesome step-up in
responsibility and accountability that marks the transition
from being a student to being a physician.
Cornerstones for a successful transition and more meaningful learning experience depend on the following:
Organization
Have a system that you use consistently to track
patientsa system detailing everything from a patients
birthday to medical history (use notecards, sheets of
paper, or a personal digital assistant).
Record and keep accessible your patients medical histories and pertinent lab and other data (you never know
when a clinical situation or an attending physician will
insist that you know this information).
Attention to detail
Be able to explain every abnormal clinical finding,
abnormal lab result, or abnormal test result.
Be the first one who finds out these results.
Time management
Patient care comes first, but always find a way to
complete everything before attending rounds or
conferences. Note: conferences and rounds will provide
the fundamental knowledge base you will need to gain
confidence and independence.
If you are consistently behind in your work in the
mornings, you need to learn ways to be more efficient
Special abbreviation used in this chapter: PRN, as needed; q, every; qid, 4 times
daily; tid, 3 times daily.
989
you should not sacrifice your education (i.e., missing

conferences) to complete your morning rounding.
Be mindful of work hour rules and do not violate them.
ROUNDS AND NOTES
Prerounds
Before meeting with the senior resident each morning, it is
critical that the successful first year resident preround on all
of his or her patients.
This means
Finishing all progress notes on each patient
Personally reviewing all the patients radiology studies
Reviewing and interpreting all the patients lab values
Writing all initial daytime orders
The senior resident is an invaluable resource who will be
eager to help you organize your thoughts, to interpret the
data, and to teach you the mechanics of residencytake
advantage of his or her experience.
You are at a point in your career where the team will base
management decisions largely on your daily subjective and
objective evaluation of the patient.
Be thorough and accurate and have a low threshold to ask
for help if you do not understand an issue.
Because patient care is primarily the interns responsibilityand patient care is the primary method of learning and
becoming a well-rounded and efficient physicianconsistently relying on the senior resident to help you catch up limits your growth and suggests the need for you to find innovative
ways that improve your efficiency and foster patient care.
The occasional use of the senior resident to round on
unseen patients because of unforeseen complications is
acceptable and appropriate.
Each patient should be seen before you attend rounds.
Afternoon Rounds and Addendums
Round on the patients in the afternoon to follow up on lab
results and to discuss with the patients and their families the
new data or the plans that have been delineated.
Because the chart is a communications tool, it is generally
suggested that a very brief addendum note be left every afternoon updating the patients clinical course.
990
V INSIGHTS
Remember that your colleagues (who are less familiar with

your patients) may need to review the chart on cross-over
to deal with an important issue that occurs overnight.
Therefore, it is imperative to leave an addendum note whenever
Lab data return that require interpretation or explanation
e.g., was the thoracentesis specimen consistent with a transudate or exudate? Was the patients decrease in hemoglobin an anticipated response to volume resuscitation?
Lab or other data return that will alter the treatment plan
e.g., CT confirmed the presence of a large pseudocyst that
requires drainage
Discussions occur with the patient or family about prognosis, code status, etc.
Any important change in the patients clinical status that
changes the clinical plan from the morning note, e.g., newonset atrial fibrillation with rapid ventricular rate requiring moving the patient to a monitored bed
Progress Note Etiquette

Progress notes are meant as a tool to communicate your evaluation, treatment plan, and rationale behind the work-up and
treatment.
Progress notes are not a place to document grievances or
complaints.
It is inappropriate to leave notes in the chart that document disapproval or irritation with other members of the
care team (nurses, consultants, the patient, etc.).
Always maintain a professional and neutral demeanor in
your writinga demeanor that reflects scientific thought
and consideration rather than personal feelings about
others.
ADMISSIONS AND ORDERS

Multiple Admissions at the Same Time
Frequently, multiple admissions arrive on the floor simultaneously.
Always see the sickest patients as a priority, and initially
take a very brief history and perform a targeted physical.
991
Enter initial orders in the chart so that treatment can begin,

and then see the next patient.
Your write-ups should be done only after every patient has
been seen and has orders on the chart.
Patient care is primary, with documentation secondary.
The senior resident can help you divide and conquer when
several patients arrive at the same time; however, you are
ultimately responsible for the admission orders and treatment plan for all your admissions.
Orders
No standardized format exists for admission orders, but most
residents prefer to use ADDCC-VAN-DISMAL as standard,
as follows:
Assign as (inpatient/outpatient observation) status to ___
team (details about appropriate inpatient vs. outpatient
assignment are in the next section).
Include the service name, the attendings name, and
then your name and pager number
You must also decide on the bed typedoes the patient
require a monitored bed (telemetry), regular medical
bed, surgical bed, oncology bed, orthopedic bed, ICU
bed, etc.?
DiagnosisThe patients preliminary diagnosis; this does
not have to be exact but should offer nursing and other
staff a working idea of the patients main diagnosis.
Deep venous thrombosis prophylaxisone of the most
important, avoidable, hospital-acquired complications is
deep venous thrombosis or venous thromboembolism.
Discuss with your senior resident if the patient is a candidate for pharmacologic therapy (such as low-molecular-weight heparin) or mechanical prophylaxis (antiembolic hose or alternating compression devices).
ConditionFair, stable, unstable, critical, etc.
Code statusEvery patient should have a code status
notation (in some states, this is considered the law).
If a patient opts for any condition other than full code,
a notation must be made in the chart (see the section
on DNR orders below).
Vital signs
If you order vital signs hourly, you should also check on
992
V INSIGHTS
the patient that frequently.

Also consider the patients comfortdo you actually
need the patients vital signs at 2:00 AM?
Standard frequencies vary from every (q) 4 to q 8 hours,
but you can also add WA to signify that you want
vital signs obtained only while the patient is awake.
There is a difference between tid and q 8 hours and
between qid (4 times daily) and q 6 hours, etc.; anytime you specify q x hours, the lab, medication, glucose check, and so forth, will occur precisely separated
by x hours. The other times, e.g., tid, are performed at
standardized times (e.g., 0700, 1300, 1800 hours).
Allergies
Distinguish between allergies and untoward side effects.
For example, hives are allergies, and a little dyspepsia
is probably a side effect.
Be sure to list the type of reaction the patient has to the
drug in question (e.g., penicillin causes rash) because this
can guide other physicians drug choices.
NursingRequests such as aspiration precautions, fall
precautions, and seizure precautions should be listed here.
DietThis will be the first thing you will be called on
for most patients (see Diets section below).
Ins/outs
Requests for strict accounting of the patients ins/outs
are made here.
You can also specify IV fluids and flow rates as well as
the need for catheters here.
Avoid giving IV fluids without an indication and avoid
fluids that are running at To Keep Open rates because
this essentially attaches the patient to an IV pole, usually with a beeping flow regulator that is sure to disgruntle the patient.
You can request that an IV be capped, i.e., IV access
is present but drips are not.
SpecialOther miscellany can be ordered in this section,
such as ambulating pulse oximetry. Consider physical,
occupational, and speech therapy as warranted.
993
Medications
Medications preferably should be listed by generic name.
Be sure to include PRN (as needed) medications to
cover possible contingencies as warranted (e.g., sleeping medications, laxatives).
Order only medications you think can be given safely
to the patient.
A good mental exercise and practice is to check for
drug-drug interactions if you intend to prescribe more
than three medications.
Most personal digital assistant programs and online
programs such as Micromedex offer an engine that
checks for pertinent reactions given a set of medications.
Activity
All patients should have an order encourage ambulating tid while in the hospital unless you can think of a
contraindication (acute myocardial infarction, newonset seizures, mental status change, etc.). Patients
who cannot ambulate should be up to a chair tid. This
helps decrease the risk of deep venous thrombosis developing and maintains or improves the patients conditioning.
Labs/radiology
Order only tests needed to confirm or to rule out a
diagnosis.
Avoid ordering shotgun daily labs, which can markedly
increase the costs of hospitalization and can lead to the
need for a secondary work-up to explain an unexpected
abnormality.
Outpatient vs. Inpatient Status

What it Means
The guidelines for what constitutes outpatient status or
admit status are beyond the scope of this handbook (especially because they are a continually moving target and
vary by diagnosis), but some general notes are included
below.
Assignment of the appropriate status is not trivial.
Improper patient status assignment costs hospitals billions of dollars annually and results in very large hospital
billsnot covered by insurance.
994
V INSIGHTS
Take assignment seriously, and do not merely guess.
Ideally, if there is some issue about which status is the
better one, discuss the case with a case manager; the senior
resident may also be able to help guide you with making
this difficult and frequently nebulous decision.
In general, outpatient status is reserved for
Semiurgent work-up requiring low-level but constant nursing care for a low-risk diagnostic group
Hospitalization of no more than 48 hours
Patient status should be upgraded from outpatient to inpatient if the work-up intensifies, the diagnosis becomes higher acuity, or hospitalization will be longer than 48 hours.
In general, inpatient status is reserved for
Urgent or unstable patient work-up requiring intensive
nursing care or monitoring and considerable medical intervention for a high-risk diagnostic group
Hospitalization of any length of time, even <24 hours
Patients cannot be reclassified to outpatient status if the
inpatient criteria are not met.
The Details
Outpatient status generally is used to complete a semiurgent work-up or treatment that requires low-level, but constant, nursing care (e.g., atypical chest pain for a low-risk
patient with active bleeding of lower gastrointestinal tract).
Outpatient status expires after 2 hospital days (i.e., 48 hours
from the time of the admission order).
After the end of 48 hours, patient status should be changed
from outpatient to inpatient; otherwise, the test or the hospitalization may not be covered by Medicare or insurance.
Any patient who requires major medical intervention
(myocardial infarction, stroke, diabetic ketoacidosis, etc.),
intensive nursing care, or specialized monitoring should be
admitted formally on an inpatient status.
Patients also should be on an inpatient status if they are
admitted with any kind of IV drip (heparin, insulin, nitroglycerin, etc.) except for routine fluids or if they require
ICU monitoring.
995
All hospital-to-hospital transfers are considered inpatient

status.
Direct admissions (admissions to the floor that bypass the
emergency department by physician order) tend to be inpatient status.
Although outpatient status can later be changed to inpatient
status, once a patient is assigned inpatient status, he or she
can never be switched to outpatient status.
Many physicians (residents and staff) opt for outpatient status as default because it offers flexibility.
However, if used incorrectly, the hospitalization may
not be covered by insurance or Medicare and this can
adversely affect both the hospital and patient financially.
In summary, assigning proper admission status is complicated and a constant challenge for physicians, case managers, and patients.
Take this part of your orders seriously, and consult with the
case manager or senior resident whenever you are in doubt.
Diets
As soon as the patient gets to the floor, the nurses invariably
will contact you for a diet order regardless of how sick the
patient is. Use your judgment carefully.
Some choices for diet include the following:
Strict NPO
This unnecessarily severe order is needed only for
obtunded patients or for patients in whom any PO intake
may worsen their care (such as acute dysphagia or recent
throat surgery).
Use it sparingly.
NPO except for medications, sips, and ice chips
This is an ideal option, allowing patients to have sips of
water, ice chips, and their medications.
Even patients scheduled for esophagogastroduodenoscopy, surgery, etc., can generally have this diet.
Use this order when you are not sure whether the patient
should eat.
xxxx kcal American Diabetes Association diet:
The diet for diabetics
You should calculate the patients caloric needs.
996
V INSIGHTS
Renal dieta low phosphate, low potassium, low residue
diet for patients with renal failure
Cardiac diet
A low sodium, low fat diet
You can specify no sodium or 2 g sodium daily
options.
Clearsbasically only water-based, thin liquids such as
broths, Jello, and tea
Soft diet
A diet that is easily digested and contains more calories
and substance than a clear diet
Includes apple sauce, thicker soups, etc.
A good choice as a transition diet for patient who is
starting to eat after a long time of NPO, etc.
Thickened liquid or pureed
This diet usually consists of pureed food.
It is ordered for patients who tend to aspirate or cough
when they eat.
Although usually ordered by speech therapy, it is a reasonable choice if you believe the patient is at high risk
for aspiration on basis of history.
Be creative
Combinations of diets (renal + cardiac) can be ordered.
Remember that the more limitations you place on a
patients diet, the more likely the food is to taste bland, and
the more likely the patient is to protest.
Make sure your choice of diet is medically necessary, and
discuss with the patient why you may be limiting his or her
dietary choices.
Notify the Patients Primary Care and Other Outside

Physicians
This is a critical aspect of admitting the patient.
Primary care physicians are often able to provide historical details a patient does not remember about previous
work-ups or diagnoses.
Furthermore, patients frequently need reassurance that
their physicians are involved in their care.
997
Regular updates and notification before discharge are

essential parts of patient care.
Writing Up the History and Physical

Write-ups may vary by institution.
An approach is suggested below:
Chief complaintUse the patients words.
Reason for admissionone line stating the physicians
assessment why the patient needed to be admitted to the
hospital
History of present illness
Thorough but concise summary
Can include lab data, previous work-up, etc., if it is
critical part of patients history
A history of present illness should guide the reader or
listener toward the diagnosis. Do not withhold data for
dramatic effect; think of the history of present illness as
a preemptive argument defending your ultimate conclusions (that you will detail in your diagnosis).
Past medical history
A chronologic summary is best.
Include pertinent supporting details that help provide a
contextual idea of disease severity.
For example, if the patient has a history of heart failure,
the date of the last echocardiogram, with the ejection
fraction and wall motion abnormalities, is helpful. For
diabetes, you should include the last hemoglobin A1C
and evidence of end-organ damage (retinopathy, last
creatinine, neuropathy, history of diabetic ketoacidosis, etc.).
For patients with a history of malignancy, it is essential
to outline the dates and types of chemotherapy and
radiotherapy, surgery, and adverse events.
This exercise also educates you about the patient and
allows you to be more prepared for rounds and decisions on treatment plans.
Past surgical history
A chronologic summary is best.
Try to include dates, institution where the operation
was performed, indication, and complications.
Allergies
998
V INSIGHTS
Write the generic name of the medication and the type

of reaction the patient had.
This will ensure the delineation between allergy (e.g.,
urticaria, wheezing) and side effect (e.g., nausea,
diarrhea).
A side effect should not be recorded as allergy but
as medication intolerance.
Medication intolerances (see above)
Medications
List all the patients medications (try to use generic
names because they offer more clarity and less commercial bias).
Be sure to inquire about and include over-the-counter
medications, eye medications, and herbal supplements,
which patients may not consider medications.
Family history
List only pertinent history, e.g., if the patients father died
at age 99 of old age, this is probably superfluous.
List histories of early cardiac disease, diabetes, bleeding history, familial disease, and cancer history.
Use judgment, e.g., an 88-year-old being admitted for
unstable angina has outlived his or her familial cardiac
risk.
Noncontributory can be used for these and similar
circumstances.
Do not mark the family history as negative without
specifying for what it is negative (e.g., family history is
negative for diabetes or malignancy).
Social historyInclude marital status, smoking history,
drug history, ethanol use (including response to CAGE
questions), travel history, pet or animal exposures, and
occupational exposures.
Review of systems
By necessity, be brief.
List items that are pertinent but not listed in the history
of present illness (such as fevers, chills, night sweats,
weight changes).
Physical exam
999
Include vital signs.

Document only what you examined.
Include negative findings when pertinent.
Lab data
Limit to pertinent results
Circle all abnormal values.
Radiographic data
List your impressions of the radiographic studies.
Avoid relying solely on the radiologists report.
MiscellaneousInclude ECG interpretation, etc.
Assessment and plan
Make a problem list that includes all the abnormalities
you have found.
This important exercise is necessary for an intern.
Avoid early closure such as listing a problem as cardiac
ischemia if the patient has chest pain because cardiac ischemia infers a purely cardiac etiology.
Be as general as possible and list the likely differential
diagnosis for each problem.
Justify your reasoning on the basis of the data you have.
You do not need to make a diagnosis on admission.
A problem list allows you to consider items in the differential which would otherwise be missed.
Furthermore, problem lists, rather than stabs at diagnosis, facilitate learning.
One approach is to divide each problem into the following:
Differential diagnosis
Most likely cause of the problem
Other potentially lethal causes that need to be excluded
Rare and unlikely diagnoses that will be considered if
the initial work-up is negative
Diagnostic plan
Your plan needs to justify every test you are planning to
order, accentuating the clinical importance of the data
you hope to obtain.
This ensures that other physicians (consultants or crosscovering residents) will know what your overall plan is,
e.g., Will order CT of abdomen (rule out diverticulitis
vs. neoplasm) that may prompt invasive evaluation (such
as a flexible sigmoidoscopy) depending on these results.
Treatment plan
1000
V INSIGHTS
What medicines and other treatments you intend to use
in the meantime
CHECKOUT
Nothing can be more challenging on a call night than providing cross-over for other residents patients about whom you
know little.
Although some programs have night-float systems, many
programs continue to have on-call residents provide nighttime cross-over.
To improve your call nights, and those of your colleagues,
you should commit to the following golden rules:
Leave No Work Unfinished

You should avoid checking out work to the cross-over team,
because the team will be busy with admissions and will not be
sufficiently familiar with your patients to provide routine care.
If you order labs or radiology studies late in the day, make
sure the on-call team knows what tests they are and how you
would manage the results.
You are ultimately responsible for your patients and their care.
Be efficient but mindful of work hours. You should never violate your programs work hour rules. Develop plans to make
you efficient at care while you are scheduled to work in order
to improve patient care and to decrease the on-call workload of colleagues.
Try to Avoid Writing Call M.D./House Officer If...

Orders
Frequently, physicians will write orders for nurses to call
the on-call M.D. It is best to limit writing these orders unless
you also have thought of what the on-call M.D. should do
with these data. If you think you need to place an indication
for calling the M.D. (sometimes it is essential, e.g., for a
hemoglobin <8.0 g/dL in a patient with gastrointestinal tract
bleeding), indicate in your progress notes or history and
physical what you are monitoring and why. This is extraordinarily helpful for cross-over.
1001
Your goal is to minimize your colleagues distress in the

middle of the night by anticipating what should be done with
these results.
You may either point out your plan of action during checkout or you may write orders to handle these potential eventualities (such as a PRN sliding scale of insulin for high levels of blood glucose).
This does not mean the on-call team should not be disturbed
at all; matters of patient care are paramount.
Your job is to try to limit unnecessary telephone calls
(especially those that could interfere with sleep) by restricting notify orders to necessary or pertinent concerns
only.
Talk With the Patients Nurse and Family

Before leaving for the day, talk with the patients nurse to
make sure no issues of concern remain (there will frequently be minor questions the nurse would like to ask or clarify,
and if the nurse does not get to ask you, she or he may have
to call the on-call team who do not know your patients well
enough to answer most questions).
It is especially important to discuss the current work-up
information and subsequent treatment plan with the patient
and the patients family before you leave for the day.
PRN Orders
Be sure to have PRN orders written for constipation, diarrhea,
dyspepsia, insomnia, and pain, as you deem reasonable.
Nothing is more disruptive than answering a call at 3 AM
because a patient needs a sleeping pill.
However, if you have concern about ordering a sleeping pill
(e.g., a patient with hypoxia who hypoventilates), relay
this to the nurse, write an order explaining that you wish
to avoid sleeping pills for the patient, and document it in
your progress notes.
Remember, if you are trying to avoid giving a PRN order
for a certain problem, you should also communicate that
at checkout.
Checking Out
When you transfer care to the on-call team, be sure to include
1002
V INSIGHTS
code status and active problems for which the on-call team
may be notified.
It is helpful to know what antibiotics a patient is taking and
what you would like the on-call physician to do if a fever
develops.
You should provide the on-call team with an updated patient
list; be sure to update the patients problems to accurately
reflect current issues.
Once the on-call physician feels comfortable, you can leave
and you should turn off your pager.
CONSULTS
Curbside Consults
If you have a brief, general question you think can be
answered without a consultant actually seeing a patient
(e.g., What is the best treatment for ACE-inhibitorinduced
coughs?), contact an on-call physician for a curbside
consult.
Curbside consults should be brief, general, and require minimal knowledge of the patient by the consultant.
Do not write the curbside consultants name in the chart
(Discussed case with Dr. Smith who said...) because the
consultant has not seen the patient and provided only general
information.
Putting the name of the consultant in the chart unfairly
increases his or her liability especially since he or she has
not had an opportunity to interview or examine the patient.
Formal Consults
Always discuss obtaining a formal consult with your senior
resident and/or attending before requesting one.
Before requesting a consult
You and the senior resident should formulate a specific
issue the consultant is asked to evaluate.
You should have begun or completed a basic work-up
before calling the consultant so that you will be able to
provide him or her critical data (and potentially to answer
the question yourself, avoiding the need for a consult).
1003
You need to ascertain if the consult must be done with the

patient in the hospital or if it can be safely deferred until
the patient is discharged.
Remember, just because the patient is in the hospital
does not mean that all his or her medical issues and
consults need to be completed before discharge.
As part of the daily progress note about the patient or as
an addendum, you must make a clear notation in the chart
about the specific information you want from the consulting service.
Consults should be requested as early in the day as possible, particularly on weekends.
Avoid calling for consults during the middle of the night
unless an emergency exists.
Proper use of consultants will result in an environment conducive to learning and teaching.
Example of an improper consultThe patient is short
of breath and we do not know why. Could you look at
the patient and tell us?
Example of a proper consultThe patient is short of
breath and hypoxemic. His alveolar-arterial gradient is
widened, but a ventilation-perfusion scan was normal. He
continues to worsen. Attempts at improving oxygenation
have failed, and he now is requiring a 50% Venturi mask.
We would appreciate your help with diagnostic and treatment suggestions about his hypoxemia.
PROCEDURES
Informed Consent Forms
Obtaining informed consent means educating the patient
about the benefits and risks of having a procedure performed
before he or she authorizes you to perform the procedure.
All procedures more invasive than a simple IV require that
an informed consent form be signed by the patient or the
patients proxy.
It is important to have the patient repeat to you the potential
risks and benefits before signing the form.
It is also important to know that this form means only that
the patient is aware of potential risks, not that he or she is
relieving you of any liability if an unforeseen complication
occurs.
1004
V INSIGHTS
Procedure Notes
After completing a procedure, you need to document the
procedure in the progress notes or to dictate the procedure,
depending on your hospitals protocol.
A suggested format follows:
Procedure performedself-explanatory
IndicationSummarize in one or two words.
Consent
The patient (or proxy) signed an informed consent
form after the potential risks (bleeding, hemorrhage,
etc. [list them]) and benefits (definitive diagnosis and
treatment, etc.) were discussed at length and the patient
was able to verbally repeat these to me. All questions
about the procedure were answered to the patients
satisfaction.
OperatorsList yourself and whoever is supervising or
assisting you.
TechniqueThe patient was prepped and draped in the
usual sterile fashion. Using aseptic technique...
Give a cursory summary of the procedure, such as ...a
TLC was advanced over the wire using aseptic Seldinger
technique into the right IJ.
This does not need to be particularly detailed unless
there were complications.
Assuming there were no complications, close with,
There were no immediate complications, and the
patient tolerated the procedure well.
Estimated blood lossGuess the amount, but always list
some value (often, the author lists <5 mL if the blood loss
was not appreciable).
DispositionNote here if you checked a chest X-ray, if the
patients pulse was present distally, if the patients ports
flushed easily, etc.
Complications
Rarely, complications occur.
Be sure to document them neutrally and factually in the
chart and what was done about them.
1005
The senior resident and attending must be informed

promptly and will help guide how the complications will
be presented to the patient and family.
CHANGE OF SERVICE
Off-Service and Transfer Notes
Whenever a patient is transferred from one service to another or whenever you are leaving a service (e.g., at the end of
a rotation), it is an act of courtesy for you to provide a detailed
note.
These notes should be handwritten because of the delay
between dictation availability and the time the accepting
service needs to access the information.
A recommended format is as follows:
Date of admission
Reason for admissiongeneral problem that led to admission
Primary care provider(s)This helps the accepting resident know with whom he or she needs to coordinate discharges or changes in condition.
Hospital course
Briefly describe the patients hospital course,
summarizing all studies (radiology, echocardiography,
etc.) that were performed and why they were performed.
Detail the reason behind the addition or subtraction of
any medications.
Summarize surgical procedures and their findings or
complications.
Try to include specific diagnoses and treatments,
responses to therapies, and adverse outcomes.
Try to avoid restating procedures and findings previously noted in the summary, rehashing the patients
hospital course day by day, and including insignificant
(e.g., transient constipation) or too much data.
Remember, clinicians can review the chart if more
detailed information is needed.
Pertinent physical findingsSummarize key abnormalities.
Consulting servicesIndicate which services have been
consulted and which are still following the patient.
Current medications
List all current medications.
When listing antibiotics, list the antibiotic day number.
1006
V INSIGHTS
Active problem listOutline the patients current problem list and goals before discharge (if appropriate).
Code status
Acceptance Notes
The point of writing an acceptance note is not to rehash verbatim your colleagues off-service or transfer note but to
document your own physical exam and create your own
problem list.
Above transfer note/off-service note by Dr. _______
reviewed and discussed with the patient and his/her
family.
Current physical examPerform a complete exam as you
would normally.
Current problem listFormulate your own assessment
and plan.
Code status
DISCHARGES
On Admission
Begin discharge planning on the day of admission.
Try to anticipate special needs the patient may have on
discharge because some needs may take several days to coordinate.
Will the patient need a home health nurse?
Will the patient need physical therapy after discharge?
Will the patient require dietary education (new-onset
diabetes)?
Will the patient need home physical and occupational
therapy?
Request that a nurse case manager assist you in discharge
planning.
The case manager is a critical aspect of the patients care; he
or she will help find placement for the patient and will also
handle all insurance matters relating to the hospitalization.
The case manager will arrange for health care, hospice, and
nursing home.
1007
Including case managers as early as possible in the hospitalization improves disposition planning considerably.
Days Before Discharge

Be proactive in discussing matters of follow-up with the primary care physician before discharge.
The patients primary care physician may have very specific instructions for follow-up arrangements (such as tests,
consults, and appointment dates).
It is your responsibility, not the patients, to make these
arrangements.
Discharging Patients Home

To discharge a patient to home, you need to complete four
things:
Prescriptions
An interdisciplinary discharge instruction sheet
Scheduled follow-up with the primary care physician
A discharge order
Prescriptions
Give patients prescriptions for medications that have been
changed or added during the hospitalization.
You may give a 30-day supply with one refilladditional
refills must be through the patients primary care physician.
Interdisciplinary Discharge Instructions

The format of this sheet varies by institution, but it usually
contains the following information:
Follow-upSpecify the physicians with whom the patient
is to follow up and the dates and times.
DietLeave specific recommendations (low salt and
low fat instead of cardiac).
ActivityFill in restrictions (no driving until cleared by
your primary doctor) or encourage a resumption of normal exercise.
Studies have shown that a written exercise prescription
increases patients adherence to exercise.
Medications
Write down all the patients medications (even if they have
1008
V INSIGHTS
not been changed), and be sure to write both the generic and
brand names along with the pill dosage and frequency.
This sheet goes home with the patient, and many patients
refer to this for their pill schedule; therefore, directions
for taking the medications and their frequency must be
written in plain English.
Do not write, Furosemide 120 mg PO every AM, 60
mg PO every PM.
Do write, Furosemide (Lasix) 40 mg 3 pills every
morning and 1 1/2 pills at night.
Scheduled Follow-up With the Patients Primary Care
Physician
Continuity of patient care is essential when transitioning a
patient to the outpatient environment.
Although most patients probably are responsible enough to
schedule a follow-up visit with their primary care physician,
some may not know that this is important.
Failure to schedule appropriate follow-up may expose you to
considerable liability if anything adverse occurs to the patient.
Discharge Order
As intuitive as it may seem, you need to write a discharge
order before a patient can be discharged.
Home Health Care Orders

Patients going home with home health care will need orders
documenting specific things they are requested to do.
It is paramount that you name the attending physician who will
be responsible for telephone calls from the home health nurse
and for all the paperwork regarding the home health visits.
Home health orders
Attending for home health will be Dr. ________. This
should be a physician who will be responsible for the
patients outpatient care (e.g., a primary care physician) and not your attending on an inpatient service.
1009
This doctors office telephone number is __________.

Medication orders
List all medications and dosages.
Miscellaneousincludes some or all the following:
Home physical therapy, occupational therapy, speech
therapy
Home safety evaluation
Medication administration
Vital signs assessments
Social worker evaluation
Insulin teaching and monitoring
Administration of IV medication
Central line care and dressing changes
Wound care and dressing changes
Hospital beds, bedside commodes, etc.
Notification of the Primary Care Physician

You should call the primary care physician on the next business day to discuss the care rendered and the patients disposition issues.
Discharge Summaries
Primary care physicians rely on discharge summaries for
understanding what happened to the patient during the hospitalization.
These should be completed on the day of discharge.
Brevity is the key to an effective summary; almost all the
important information should appear on the first page.
Requirements vary by institution; the following template is
recommended:
Date of admission
Date of discharge
Discharge diagnoses
Include only the important diagnoses and comorbidities
Always number them from most to least important, if
possible.
Procedures performed
List all procedures.
If the procedure was for diagnostic purposes, include the
pertinent data found (e.g., Lumbar punctureCSF
was normal except for a high protein at 58).
1010
V INSIGHTS
Other pertinent findings

List other grossly abnormal physical or lab findings.
Treatment rendered and hospital course
Give a very brief synopsis of the hospital course.
Try to include specific diagnoses and treatments,
responses to therapies, and adverse outcomes.
Try to avoid restating procedures and findings previously noted in the summary, rehashing the patients
hospital course day by day, and including insignificant
(e.g., transient constipation) or too much data.
Remember, clinicians can review the chart if more
detailed information is needed.
DispositionState where the patient is going: to home,
to hospice, to nursing home, etc.
Discharge medications
This is critical.
Include doses and frequency.
Do not forget that oxygen is a medication.
DietList fluid restrictions or specific dietary restrictions that are not immediately obvious.
ActivitySpecify if the patient has specific restrictions
(driving restriction, lifting restrictions, etc.).
Follow-upList with whom patient has follow-up and
the dates and times.
Carbon copies
Include all physicians who care for the patient outside
the hospital.
For out-of-town physicians, be considerate of the transcriptionist and include the office address, telephone
number, and fax number of the clinician.
Patients cannot receive copies without going to medical
records and specifically requesting them.
HOSPITAL DEATHS
Pronouncing a Patient
There is no standardized format for doing this. However,
you should feel no palpable pulse, you should not be able to
auscultate breath or heart sounds, you should note no response
1011
to deep pain, and you should note no pupil response to light.

When the patient meets the criteria of death, you should
notify the nurse of the time of death (which is the time the
patient is pronounced) and make a notation in the chart.
Be compassionate and professional, especially when the
patients family is present.
It is important to tell the family that the patient has died
rather than using euphemisms such as expired or passed
away.
Who to Contact
The nursing supervisor will be notified of all deaths by the
nurses and will handle all the paperwork and details (such as
mortician transfer and organ donation).
You should discuss the death with the family if any are present.
If the family is not present, the decision about how to inform
them should be made by the senior resident or attending.
Generally, it is always better for the family to be told in person.
A chaplain usually is available 24 hours a day and is trained
in dealing with most religious persuasions.
Ask the unit secretary to page the on-call chaplain if the
family desires religious help.
Allow the family as much time with the body as needed and
be available for questions until the family leaves.
Avoid speculating on the cause of death except in general
terms, and if you are unsure of the cause, be honest and say
so.
Autopsy Requests
Patients who die in the hospital may have an autopsy performed with the familys permission.
For learning or determining the possible pathologic basis
for death, it is nearly always important to ask the family for
an autopsy.
Autopsies can be partial (such as a limited brain autopsy)
and can be coordinated with the morticians.
Most teaching institutions do not charge for an autopsy performed on patients who die in the hospital.
It may help to tell the patients family that this is a nonmutilating, precise surgical procedure to explore why the patient
may have died.
1012
V INSIGHTS
You may also suggest that findings from an autopsy may be the
ultimate gift and an unparalleled opportunity to educate
physicians, improve subsequent patient care, and provide possible diagnoses that were not clinically apparent before death.
It is important to reassure the family that an autopsy will
not preclude an open casket funeral and generally will not
delay burial.
Understand that the patients family may have objections,
and do not push too hard.
You should attend autopsies on your patients if possible.
Organ Donation
Laws vary by state on whether physicians may approach
families to request organ donation.
Check with your nursing supervisor or hospital attorney
about the law in your area.
Frequently, highly qualified persons with an organ procurement team are best able to approach the patients family
about this topic.
Deceased patients can still be organ donors for corneas, ligaments, and bone.
Body for Science

Patients and families may wish to donate the patients body
to science.
This may range from an extended autopsy for educational reasons to cadaveric donation.
Ask the on-call nursing supervisor or case manager to arrange
for this generous act.
Your Own Emotions

After a patient dies, you will often be confronted with your
own doubts about treatment or will be saddened by the loss
of someone about whom and for whom you cared.
You are encouraged to discuss these feelings with your colleagues, attending, or program director.
All in-hospital deaths on academic services will be addressed
at a monthly morbidity and mortality conference aimed at
1013
learning what, if anything, may have been done differently

to improve patient outcomes.
This conference is a supportive atmosphere to discuss
your own concerns about management and to grow as a
clinician.
Death Summary
Date of admission
Date of deathThe date the patient was pronounced.
Reason for hospitalizationList the medical reason the
patient was hospitalized.
Treatment rendered and events leading up to death
Give a very brief synopsis of the hospital course.
There is no need to give extensive detail because the death
summary will not be used by other physicians.
Try to include only major pertinent observations in a
chronologic order ending with the patients death.
1014
V INSIGHTS
PREOPERATIVE MEDICAL EVALUATION
Ripudamanjit Singh, M.D.
Charanjit S. Rihal, M.D.
GENERAL GOALS
To identify unrecognized comorbid disease and risk factors
for medical complications of surgery
To optimize preoperative medical condition
To foresee, prevent, and treat potential complications
PRINCIPLES OF CONSULTATION
Restrict advice to the internists unique areas of expertise, e.g.,
advise on perioperative insulin management but leave anesthetic technique to the anesthesiologist.
Keep number of recommendations to a minimum.
Adherence to recommendations diminishes for consults
with more than 5 recommendations.
Follow patients through the postoperative period because
many perioperative complications occur during this time.
Correct documentation.
The preoperative patient is not being cleared. This may
incorrectly imply there is no risk; rather, the evaluation
may determine that the patient is at average risk for the
proposed procedure, which should be documented in
your note (if no factors are found which increase perioperative risk).
Modern anesthesia is extremely safe.
Patient and surgical factors are more important risk predictors than anesthetic considerations.
The American Society of Anesthesiology classification is
a powerful predictor of overall perioperative mortality; it
also predicts cardiac and pulmonary morbidity (Table 1).
Special abbreviations used in this chapter: CABG, coronary artery bypass graft;
MET, metabolic equivalent; PTCA, percutaneous transluminal coronary angioplasty.
1015
Table 1. American Society of Anesthesiology Classification

Class
1
2
3
4
5
E
Systemic disturbance
Mortality, %
Healthy patient with no disease outside

the surgical process
Mild-to-moderate systemic disease caused
by the surgical condition or other pathologic processes
Severe disease process that limits activity
but is not incapacitating
Severe incapacitating disease process that
is a constant threat to life
Moribund patient not expected to survive
24 hours with or without an operation
Suffix to indicate emergency surgery for
any class
<0.03
0.2
1.2
8
34
Increased
PREOPERATIVE EVALUATION OF HEALTHY PERSONS

Perioperative risk is very low for healthy persons.
Estimated at f0.03%
Additional evaluation will have a low yield and high likelihood of false-positive results.
History is the most important factor in evaluation of healthy
persons.
For patients <40 years with normal history and physical
exam findings, no additional testing is needed.
Good exercise capacity generally predicts a low cardiac and
pulmonary risk for surgery.
SPECIFIC TESTS
CBC
Anemia is present in 1% of asymptomatic patients.
Blood loss is common during major operations.
Baseline value may be helpful before major operations.
Electrolytes
Incidence of unexpected abnormalities is <1%.
Not routinely recommended
Renal Function
Renal insufficiency increases with age.
1016
V INSIGHTS
Its presence may require adjustment of the medication dose.

Recommend renal function testing for patients >50 years
and if hypotension or nephrotoxic medications are likely.
Glucose
No definite relation between asymptomatic hyperglycemia
and perioperative morbidity.
Liver Function Tests

Asymptomatic mildly abnormal liver function tests are not
associated with perioperative morbidity.
Clinical liver disease may pose a risk; these patients are identified without screening.
Tests of Hemostasis
Incidence of surgically important abnormalities in patients
without a clinical history of bleeding tendency is extremely
low.
Reserve these tests for patients with a known bleeding diathesis or an illness associated with bleeding tendency.
Urinalysis
No evidence for asymptomatic pyuria increasing the risk of
surgical site infections
Renal dysfunction is better detected with serum creatinine
level.
Not recommended
ECG
Goaldetection of previous silent myocardial infarction or
unsuspected arrhythmia that would increase cardiac risk
Recommended for
Men >40 years and women >55 years
Clinical evaluation suggesting heart disease
Patients at risk for electrolyte abnormalities
1017
Systemic disease associated with possible unrecognized

heart disease
Chest X-Ray
In one study, incidence of surgically important abnormalities
was 0.3%, with no risk factors for cardiac or pulmonary disease.
Obtain it for patients >60 years (if not done within past 6
months).
Pregnancy Test
If any suspicion of pregnancy
CARDIAC DISEASE
Most important cause of perioperative morbidity and
mortality
Guidelines for perioperative cardiovascular evaluation for
noncardiac surgery from American College of Cardiology
and American Heart Association (Fig. 1)
Overriding theme of these guidelinesIntervention is rarely
necessary to lower the risk of surgery.
Clinical Predictors
Major
Unstable coronary syndromes such as recent myocardial
infarction with evidence of important ischemic risk and
unstable or severe angina
Decompensated congestive heart failure
Significant arrhythmiashigh-grade atrioventricular block,
symptomatic arrhythmias in the presence of underlying heart
disease, supraventricular arrhythmias with uncontrolled ventricular rate
Severe valvular disease
Intermediate
Stable angina pectoris
Previous myocardial infarction
Compensated or previous congestive heart failure
Diabetes mellitus
Minor
Advanced age
1018
Start at step 1
STEP 1
Fig. 1
Need for noncardiac

surgery
Urgent or elective surgery
STEP 2
No
Coronary revascularization
within 5 years?
Recurrent symptoms
or signs
Yes
Yes
No
STEP 3
Recent coronary
evaluation
Yes
No
Clinical
predictors
Recent coronary angiogram

or stress test?
Major clinical
predictors*
1019
Consider coronary
angiography
Medical management
and risk factor
modification
Subsequent care
dictated by findings and
treatment results
Operating
room
Unfavorable result
or change in symptoms
STEP 5
Consider delay or
cancel noncardiac
surgery
Favorable result and no

change in symptoms
Intermediate clinical
predictors
Minor or no
clinical predictors
Go to
step 6
Go to
step 7
V INSIGHTS
STEP 4
Postoperative risk
stratification and
risk factor management
Operating
room
Emergency surgery
1020
For intermediate clinical predictors, go to step 6

STEP 6
Clinical predictors
Functional capacity
Intermediate clinical predictors
Poor
(<4 METs)
Noninvasive testing
Noninvasive
testing
High risk
Invasive testing
Moderate
or excellent
(>4 METs)
High
surgical risk
procedure
Surgical risk
STEP 8
Fig. 1 (continued)
Consider
coronary
angiography
Subsequent care*
dictated by findings
and treatment results
Intermediate
surgical risk
procedure
Low risk
Low
surgical risk
procedure
Operating
room
Postoperative risk stratification

and risk factor reduction
Fig. 1. Algorithm for preoperative cardiac evaluation. MET,

metabolic equivalent. *Major
clinical predictors: unstable
coronary syndrome, decompensated congestive heart failure,
significant arrhythmias, severe
valvular disease. Intermediate
clinical predictors: mild angina
pectoris, prior myocardial infarction, compensated or prior congestive heart failure, diabetes
mellitus. Minor clinical predictors: advanced age, abnormal ECG, rhythm other than
sinus, low functional capacity,
history of stroke, uncontrolled
systemic hypertension. (From
Report of the American College
of Cardiology/American Heart
Association Task Force on
Practice Guidelines [Committee
on Perioperative Cardiovascular
For minor or no clinical predictors, go to step 7

STEP 7
Clinical predictors
Minor or no clinical predictors
STEP 8
Noninvasive testing
Moderate
or excellent
(>4 METs)
Poor
(<4 METs)
Functional capacity
Surgical risk
Fig. 1 (continued)
High
surgical risk
procedure
Noninvasive
testing
Evaluation for Noncardiac

Surgery]. Guidelines for
perioperative cardiovascular
evaluation for noncardiac surgery. J Am Coll Cardiol.
1996;27:910-48. Used with
permission.)
Intermediate or low
surgical risk
procedure
Low risk
Operating
room
Postoperative risk stratification

and risk factor reduction
High risk
Consider
coronary
angiography
1021
Subsequent care*
dictated by findings
and treatment results
V INSIGHTS
Invasive testing
Abnormal ECG
Rhythm other than sinus
Low functional capacity
History of stroke
Uncontrolled systemic hypertension
Functional Capacity
Expressed in metabolic equivalent (MET) levels
Perioperative cardiac and long-term risk is increased in
patients unable to meet a 4-MET demand during most normal daily activities.
Duke Activity Status Index

Eating, dressing, walking around the house, and dishwashing can range from 1 to 4 METs.
Climbing a flight of stairs, walking on level ground at 6.4
km/hour, running a short distance, scrubbing floors, or playing a game of golf equals 4 to 10 METs.
Strenuous sports such as swimming, singles tennis, and football exceed 10 METs.
Type of Surgery
Surgery-specific risk for noncardiac operations can be stratified as high, intermediate, and low (Table 2).
Indications for Angiography

High-risk results during noninvasive testing
Angina pectoris unresponsive to medical therapy
In most patients, unstable angina pectoris
Nondiagnostic or equivocal noninvasive test in a high-risk
patient undergoing a high-risk procedure
Indications for Coronary Artery Bypass Graft (CABG)

Surgery and Percutaneous Transluminal Coronary
Angioplasty (PTCA)
Indications for CABG before noncardiac surgery are identical
to those in general.
CABG is rarely indicated to simply get a patient through
the operation.
Similarly, indications for PTCA in the perioperative setting
are the same as those for PTCA in general.
1022
V INSIGHTS
Table 2.
Cardiac Risk Level for Noncardiac Surgical

Procedures
Low risk
Breast
surgery
Superficial
procedures
Endoscopic
surgery
Cataract
surgery
Intermediate risk
Carotid endarterectomy
Head & neck surgery
Intraperitoneal surgery
Intrathoracic surgery
Orthopedic surgery
Prostate surgery
High risk
Major emergency surgery,
particularly in elderly
Aortic & other major
vascular surgery
Involving large fluid
shifts and/or blood loss
& prolonged procedures
Peripheral vascular
surgery
PULMONARY DISEASE
Postoperative pulmonary complications are a major source
of morbidity and mortality.
They are at least as frequent as clinically important cardiac
complications and contribute to prolonged hospital stay and
expense.
Risk Factors Associated With Increased Pulmonary
Complications
COPD
A 3- to 5-fold increase in pulmonary complications
In one study, decreased breath sounds, prolonged expiration, rales, wheezes, and rhonchi on physical examination
predicted a 5-fold increase in pulmonary complications.
Smoking
A 2- to 6-fold increase in risk, even for patients without
apparent COPD.
Risk is highest for current smokers and those who have
smoked within the past 1-2 months.
The risk is higher for smokers who stop or decrease the number of cigarettes within 1 month than for those who continue to smoke!
1023
Therefore, advise smokers to stop smoking for a full 8 weeks

before elective surgery
Obesity
Most studies show no increase in pulmonary complications,
even for morbid obesity.
Respiratory Infection
Bronchitis or pneumonia is a risk factor.
Delay the operation if any change in the character or amount
of sputum.
Surgical Site
This is the strongest overall risk factor for pulmonary complications.
Upper abdominal and thoracic operations are greatest risk
(20%-50%) because of splinting, diaphragmatic dysfunction from pain.
Lower abdominal operations have a lower risk (0-5%).
Duration of Surgery
Operations >3 hours increase the risk of pulmonary complications.
Preoperative Assessment of Patients At Increased Risk for

Pulmonary Complications
History and physical exam are most important.
Evaluate for exercise capacity, exertional dyspnea, cough,
and presence of above risk factors.
American College of Physicians position statement on
preoperative pulmonary function tests is the standard.
These tests are needed in all patients undergoing the
following:
Coronary artery bypass or upper abdominal operation if
patient has a history of tobacco use or dyspnea
Lower abdominal operation if patient has uncharacterized
pulmonary disease and a prolonged or extensive operation is anticipated
Head and neck or orthopedic operation if patient has
uncharacterized pulmonary disease
Lung resection
1024
V INSIGHTS
Risk Reduction Strategies
Preoperative
Cigarette cessation for at least 8 weeks
Optimize COPD or asthma.
Bronchodilators for symptomatic patients
Theophylline only if used long-term
Liberal use of inhaled corticosteroids to optimize pulmonary function
Goal peak flow of 80% of personal best or predicted
for asthmatic patients
Antibiotics only if change in character of sputum suggests infection, not warranted routinely
Begin patient education on lung expansion maneuvers.
Postoperative
Lung expansion maneuvers
Deep breathing exercises (chest physical therapy) or
incentive spirometry is preferred.
Both of above maneuvers reduce risk of pulmonary
complications by half.
Continuous positive airway pressure is equally effective
but more expensive and labor intensive.
Reserve for patients unable to cooperate with deep
breathing or incentive spirometry.
Adequate postoperative pain control greatly reduces
pulmonary complications, especially in patients who
had upper abdominal, thoracic, or aortic operations.
CORTICOSTEROID SUPPRESSION
Suspect pituitary-adrenal axis suppression in
Any patient receiving long-term corticosteroid therapy
Any patient who has had 1 week of suppressive doses
(i.e., prednisone >7.5 mg daily) within past 12 months
ACTH (corticotropin) stimulation test is usually unnecessary.
DIABETES MELLITUS
Risks include altered wound healing, presence or development
of electrolyte abnormalities, susceptibility to infection, risk
of ketoacidosis, and hyperosmolar nonketotic coma.
1025
Focus on end-organ complications, especially cardiac disease

because it is the most common cause of perioperative mortality.
Lab tests
Routine ECG, given potential for silent myocardial
infarction
Electrolytes, renal function, glucose
Urinalysis (exclude occult urinary tract infection)
THROMBOEMBOLISM PROPHYLAXIS
Stratify the risk of thromboembolism on the basis of patient
factors and type of operation (Table 3).
Very High Risk

Major operation
Age >40 years plus one of the following:
Previous venous thromboembolism
Hypercoagulable state
Malignant disease
Major orthopedic operation on lower extremity
Hip fracture
Stroke
Multiple trauma
Spinal cord injury
High Risk
Major operation
Age >60 years
None of the following clinical risk factors:
Obesity
Immobilization
Malignancy
Varicose veins
Estrogen use
Paralysis
Stroke
Indwelling femoral vein catheter
Nephrotic syndrome
Hypercoagulable state
1026
Table 3. Thromboembolism Prophylaxis According to Type of Operation*

Prophylaxis
Type of operation
Low-risk general surgery, <40
years old, minor operation
Moderate-risk general surgery, v40
years old, major operation, no
additional risk factors
High-risk general surgery, >40 years
old, major operation, additional
risk factors
Highest risk general surgery, multiple
additional risk factors
Hip replacement
1027
Hip fracture
Alternative
None
Low-dose unadjusted heparin or
LMWH or
Intermittent pneumatic compression or
Elastic stockings
Higher dose regimen of LMWH
LMWH plus
Intermittent pneumatic compression
Elastic stockings
Warfarin or
LMWH or
Adjusted-dose heparin
Warfarin or
LMWH
Intermittent pneumatic compression if

prone to hematoma or wound infection
Warfarin to INR 2-3

LMWH
V INSIGHTS
Intracranial neurosurgery
Preferred
1028
Table 3 (continued)
Prophylaxis
Type of operation
Knee replacement
Preferred
LMWH or
Warfarin or
LMWH, low-molecular-weight heparin.

*Aspirin is not recommended as prophylaxis for surgical patients because other measures are more efficacious.
Alternative
V INSIGHTS
Previous venous thromboembolism
or
Major operation
Age 40-60 years
Clinical risk factors (listed above)
or
Patients with myocardial infarction
or
Medical patients with clinical risk factors (listed above)
Moderate Risk
Any operation for patients 40-60 years old
Major operation for patients <40 years
No clinical risk factors (listed above)
or
Minor operation
Clinical risk factors (listed above)
Low risk
Minor operation
Age <40 years
No clinical risk factors (listed above)
ENDOCARDITIS PROPHYLAXIS
High-risk categoryprophylaxis recommended
Prosthetic valves (metallic and bioprostheses)
Previous endocarditis
Complex cyanotic congenital heart disease
Surgical systemic pulmonary shunts or conduits
Moderate-risk categoryprophylaxis recommended
Most other congenital malformations
Acquired valvular dysfunction (i.e., rheumatic heart disease)
Hypertrophic cardiomyopathy
Mitral valve prolapse with regurgitation and/or thickened
leaflets
Negligible risk categoryno prophylaxis recommended
Isolated secundum atrial septal defect
Surgical repair of atrial septal defect, ventricular septal
1029
defect, patent ductus arteriosus

Previous CABG
Mitral valve prolapse without regurgitation
Physiologic, innocent, or functional murmurs
Previous Kawasaki disease or rheumatic fever without
valvular dysfunction
Pacemakers
Dental procedures for which prophylaxis is recommended
Dental extractions
Periodontal procedures, including surgery, scaling, planing, probing
Dental implant placement
Endodontic root canal instrumentation
Subgingival placement of antibiotic fibers or strips
Initial placement of orthodontic bands
Intraligamentary local anesthetic injections
Prophylactic cleaning if bleeding is anticipated
Other procedure for which prophylaxis is recommended
Respiratory tract
Tonsillectomy
Surgical operations of respiratory mucosa
Rigid bronchoscopy
Gastrointestinal tract
Sclerotherapy of esophageal varices
Esophageal stricture dilatation
Endoscopic retrograde cholangiopancreatography with
biliary obstruction
Biliary tract surgery
Surgical operations involving intestinal mucosa
Genitourinary tract
Prostate surgery
Cystoscopy
Urethral dilatation
Prophylactic regimens for dental, oral, esophageal, and respiratory procedures
Standard
Amoxicilln 2 g 1 hour before procedure (no post procedure dose) or
Ampicillin 2 g IV or IM 30 minutes before procedure
Clindamycin 600 mg PO 1 hour before procedure or
1030
V INSIGHTS
Cephalexin or cefadroxil 2 g PO 1 hour before procedure (not if immediate type hypersensitivity reaction
to penicillin) or
Azithromycin or clarithromycin 500 mg 1 hour before
procedure
Allergic to penicillin and unable to take medication PO
Clindamycin 600 mg IV 30 minutes before procedure or
Cefazolin 1 g IV or IM 30 minutes before procedure.
Prophylactic regimens for genitourinary or gastrointestinal
tract procedures
High-risk patients
Ampicillin 2 g IM or IV plus gentamicin 1.5 mg/kg IV
or IM (not to exceed 120 mg) 30 minutes before procedure and
Ampicillin 1 g IV or IM or amoxicillin 1 g PO 6 hours
afterward
High-risk patients allergic to penicillin
Vancomycin 1 g IV over 1-2 hours plus gentamicin 1.5
mg/kg IV or IM (not to exceed 120 mg).
Complete injection within 30 minutes before starting
procedure.
Moderate-risk patients
Amoxicilln 2 g PO 1 hour before procedure or
Ampicillin 2 g IV or IM 30 minutes before procedure
Moderate-risk patients allergic to penicillin
Vancomycin 1 g IV over 1-2 hours
Complete infusion within 30 minutes before starting
procedure.
Approach to determining need for prophylaxis in mitral valve
prolapse
Click with no murmur or presence of murmur unknown
If emergency procedure, prophylaxis
If not emergency, obtain echocardiogram (controversial opinion).
Mitral regurgitation shown by echocardiography, prophylaxis
No mitral regurgitation shown by echocardiography, no
prophylaxis
1031
INDEX
(i indicates an illustration; t indicates a table)
A
Abdominal pain
aortic aneurysm rupture, 9, 27t
appendicitis, 9, 9t
cholecystitis, 8, 9t
differential diagnosis, 4t, 6t,
7t
diverticulitis, 9t, 10
extra-abdominal cause of, 5t
management, 8-10
pancreatitis, 9-10, 9t
risk assessment, 1-2
small bowel obstruction, 9t,
10
testing, 8, 8t
Acetaminophen, hepatomegaly,
187
Acetylcholine receptors
(ACHRs), 653, 655
Acid-base disorders, 417-429.
See also Metabolic acidosis, Metabolic alkalosis,
Mixed acid-base disorders, Respiratory acidosis,
Acid-base disorders, mixed,
418-419
Acid-base nomogram, 419i
Acute coronary syndromes,
431-449
Acute renal failure (ARF)
causes, 453t
definition, 451
dialysis, 458t
history and physical, 455t
management, 455-456, 458
mechanical ventilation, 833t
presentation, 452
prevalence, 452
testing, 454, 456t
urinalysis, 457t
Acute respiratory distress syndrome (ARDS)
mechanical ventilation, 826t,
834t
steroids, 906t
Acute respiratory failure
causes, 826t
mechanical ventilation, 825826
Admit status, 994
Aerobic bacteria, 790t-791t
Air bronchogram, 293
Air embolism, pulmonary artery
catheter, 398
Airspace-filling disorders, 293
ALP (alkaline phosphatase),
liver function test, 374t,
375, 376t, 378t-379t, 381382, 387i
Altered mental state, abdominal
pain, 1, 3
Alveolar oxygen (PaO2) equation, 283
Alveolar-arterial O2 gradient
[P(A-a)O2], 283
American College of
Cardiology perioperative
evaluation, 1019t-1021t
American Society of
Anesthesiology classification, 1016t
Aminoglycosides, 769-771,
770t, 771t
Amphotericin, 785, 786t
Amyloidosis, splenomegaly,
257
Anaerobic bacteria, 791t
Analgesic adjuvants, 863t
1033
Anemia
definition, 12
differential diagnosis, 12-19,
15t-16t
history and physical, 12-13
HIV, 564t
iron deficiency, 21, 23
macrocytic, 14t, 22i
management, 21, 23
microcytic, 13t, 20i
normocytic, 14t, 17t, 21i
peripheral smears, 19t
RBC transfusion, 23
serum profiles, 18t
testing, 19
Angina, chest pain, 56
Angina (unstable), 57
cardiac enzyme levels, 287
risk factors, 58t
symptoms, 59t
Angiodysplasia, 148
Angioedema, 243-244
Anion gap metabolic acidosis,
421
Ankle joint, arthrocentesis, 881882
Ankylosing spondylitis, 524-526
back pain, 28t, 33
Anti-CMV agents, 780, 781t
Anti-HSV agents, 778-780, 779t
Anti-influenza agents, 780-781,
782t
Anti-TB agents, 787-789, 788t
Antibacterial agents. See also
Bacterial organisms,
specific treatment
aminoglycosides, 769-771,
770t, 771t
carbapenems, 768-769, 769t
cephalosporins, 766-768,
766t
clindamycin, 776-777, 776t
(Synercid), 776t, 777
daptomycin, 776t, 778
1034
fluoroquinolones, 772t, 772-773

linezolid, 776t, 777-778
macrolides, 774-775, 775t
metronidazole, 776t, 777
monobactam, 768
penicillins, 764-766, 764t
telithromycin, 775t
tetracyclines, 773-774, 774t
tigecycline, 774t
trimethoprim-sulfamethoxazole, 775-776, 776t
vancomycin, 771-772
Antidiarrheals, 95
Antifungal agents, 784-787
Antimicrobial agents, 763-809
Antimycobacterial agents, 787789
Antiphospholipid antibody syndrome, 516-518, 519t
Antiretroviral agents, 782-784
Antithrombin, 317t, 319
Antiviral agents, 778-784
Aorta, coarctation of, X-ray,
297-298
Aortic aneurysm rupture, 9
Aortic dissection
back pain, 25-26
chest pain, 58
chest X-ray, 297
APACHE (acute physiologic
assessment and chronic
health evaluation) grading,
pancreatitis, 679
Appendicitis, 9, 9t
aPTT (activated partial thromboplastin time), coagulation panel, 308, 309i, 310t,
312t, 313t
Arterial blood gases (ABGs),
281-285
pulmonary function tests, 406,
408
Arterial oxygen content (CaO2),
282
Arterial oxygen pressure
(PaO2), 282-283
Arterial oxygen saturation

(SaO2), 281-282
Arterial pressure of carbon
dioxide (PaCO2), 284
Arterial-alveolar O2 ratio, 284
Arthritis, 194t, 195t
enteropathic, 526
mono, 191t
osteo, 191t, 192t, 197-198
poly, 192t
psoriatic, 526-527
reactive, 526
rheumatoid, 191t, 521-524
septic, 196
Arthrocentesis, 876-878
ankle joint, 881-882
elbow joint, 879
knee joint, 880-881
shoulder joint, 878-879
wrist joint, 879-880
Ascitic fluid analysis, 890t
Aspiration pneumonia, 697-698,
701
AST (aspartate aminotransferase), liver function test,
374t, 376, 377t, 381-382,
386i
Asthma. See also
Pneumothorax, Wheezing
definition, 461
diagnoses, 468-471
epidemiology, 463t-464t
exacerbation, 110, 113t, 114t,
464, 906t
management, 471-473
noninvasive positive pressure
ventilation, 838
presentation, 464-465
severity classification, 462t
Asystole, 809
ECG, 364, 366i
emergency response guidelines, 937i
Ataxia, 272, 274, 277t, 278
Atelectasis, chest X-ray, 298
Atrial enlargement, ECG, 349i

Atrial fibrillation (AF), 475-477
ECG, 358, 360i
instability, 478t
management, 479-482
thromboembolic risk factors,
483
Atrial fibrillation/flutter, emergency response guidelines,
932i, 938i
Atrial premature contractions
(APCs), 329, 330
Atrial stunning, 484
Atrioventricular (AV) blocks,
ECG, 350, 353i
Azoles, 784-785, 785t
B
B-type natriuretic peptide, 289
Back pain
aortic dissection, 25-26, 27t
cord compression, 26, 27t
differential diagnosis, 28t, 2937
disk herniation, 34, 38-39
gastrointestinal, 29
gynecologic, 29-30
hematologic, 30
infectious, 30
management, 38-39
metabolic, 30-31
musculoskeletal, 35, 38
osteoarthritis, 34, 38
psychiatric, 31-32
renal, 28t, 32
risk assessment, 25-26, 27t
spinal disorders, 28t, 33-35
testing, 37-38
vascular disease, 28t, 35
Bacterial organisms. See also
Aerobic bacteria,
Anaerobic bacteria,
Antibacterial agents
resistance issues, 806t-808t
specific treatment, 793t-802t
1035
Bacteriuria, 744t, 747

Balloon rupture, pulmonary
artery catheter, 400
Balthazar-Ranson CT Severity
Index (CTSI), 679, 681t
Benign paroxysmal positional
vertigo, 107-108
Benign prostatic hypertrophy,
162t, 168
Biliary obstruction,
hepatomegaly, 186
Bilirubin, test, 378t
Bleeding, active in anemia, 11
Bleeding disorders
differential diagnosis, 42-46
history, 45t, 46t
management, 47, 54
onset, 46t
physical exam, 46t
plasma coagulation, 45t, 49i
platelet, 43t-44t, 48i, 49i
testing, 47
types, 45t
vascular disorders, 44t
Blood gas values, 281
Blood pH, normal, 417, 419i
Body mass index (BMI), 842
Bone marrow failure, anemia,
15t-16t
Bowel (small) obstruction, 9t,
10
Bowel sounds, abdominal pain,
2
Bradyarrhythmia, 238
ECG, 352, 355i, 356i, 357i
Bradycardia, emergency
response guidelines, 935i
Breast cancer, chest X-ray, 302i,
306i
Bronchiectasis, 69
Bronchitis, 68
Bronchogenic carcinoma, chest
X-ray, 305i
Brugada syndrome, ECG, 347i
Bullous pemphigoid, 248
1036
Bundle branch blocks, 331, 333,

334i, 335i, 447i
C
C-reactive protein, 289, 751
Carbapenems, 768-769, 769t
Carbon monoxide poisoning,
oxygen therapy, 855
Cardiac arrest, 809-812
Cardiac biomarkers, 287-289
Cardiac conduction disturbances,
346-352
Cardiomyopathy
drugs associated with, 500t
HIV, 562t-563t
Cardiopulmonary resuscitation,
809, 810
Cardiovascular chest X-rays,
296-297, 203i
Cardiovascular failure, sepsis,
736-737
Cardiovascular preoperative
evaluation, 1018, 1019t1021t, 1022
Cardioverter-defibrillator,
implantable, 446
Celiac sprue, 101
Central nervous system disorders, HIV, 561t-562t,
584t-593t
Cephalosporins, 766-768, 766t
Cerebellar hemorrhage, 272, 273
Cerebrospinal fluid (CSF)
analysis, 887t
Chest compression, 810
Chest pain
causes of, 56t
differential diagnosis, 56
management, 57-58
risk factors, 58t
signs, 60t
symptoms, 59t
testing, 57, 61
Chest X-ray, 291-294
air bronchogram, 293

airspace-filling disorders, 293
aortic aneurysms, 297-298,
304i
atelectasis, 298
breast cancer, 302i, 306i
bronchogenic carcinoma, 305i
cardiovascular, 296-297, 203i
collapsed lobe, 304i, 305i
differential diagnoses, 300t301t
interstitial patterns, 294-295
normal, 302i
pleural effusion, 299
pneumothorax, 295-296
pulmonary embolism, 298,
303i
sarcoidosis, 306i
silhouette sign, 293-294
Cholecystitis, acute, 8-9
Chorea, 274, 276t
Chronic disease, anemia, 13t, 15t
Chronic obstructive pulmonary
disease (COPD), 485-488
asthma, 468
and congestive heart failure,
502, 504
diagnosis, 488
exacerbation, 109, 113t, 114t,
487t, 491t, 492t-493t,
494t, 495t, 906t
management, 488, 492t-493t,
494t
ventilation, 838
oxygen therapy, 495t, 853,
854
pulmonary function tests, 405,
406
staging, 490t
surgical risk factors, 10231025
testing, 490t
Churg-Strauss syndrome, 750t,
756-757
CK (creatine kinase), CK-MB

(creatine kinase, muscle &
brain subunits), 288, 436
Clindamycin, 776-777, 776t
Cluster headache, 153t, 156t
oxygen therapy, 856
Coagulation disorders. See also
Bleeding disorders,
platelet; thrombocytopenia
atrial fibrillation, 482-483
anticardiolipin antibodies, 320
antiphospholipid antibodies,
319
antithrombin, 317t, 319
bleeding history, 307-308
cascade, 309i
differential diagnosis, 310t
factor products transfusion,
922t-924t
factors, 312t-313t
hyperhomocysteinemia, 318t,
319
lupus anticoagulant, 320, 321t
platelet tests, 314-315
protein C, 315, 316t
protein S, 316t, 319
prothrombin, 317t, 319
screening tests, 308-314, 310t
sepsis, 738
thrombotic history, 315
Community-acquired pneumonia, 697, 700, 701-702
Compartment syndrome, 210
Congestive heart failure (CHF)
acute and chronic, 500t
chest X-ray, 296-297
comparison of types, 498t
definitions, 497
diagnosis, 503-504
dyspnea, 113t, 114t, 116
etiology, 498
Framingham criteria, 498t
hepatomegaly, 186
history, 501-502
hyponatremia, 120t
management, 505-507
1037
mimic conditions, 504-505

oxygen therapy, 853
physical exam, 502
prevalence, 501
splenomegaly, 256
treatable causes, 502t
Conjunctivitis, 223t
Connective tissue disease, 509527. See also Ankylosing
spondylitis, Antiphospholipid antibody syndrome,
Rheumatoid arthritis,
Sjgren syndrome,
Systemic lupus erythematosus (SLE)
Constrictive pericarditis, 691692, 693-694, 695
Continuous tube feeding, 846847
Contrast-induced nephropathy,
prevention, 459
Cord compression, back pain,
26, 27t
Coronary artery bypass surgery,
445
Coronary artery bypass graft
(CABG), 1022
Coronary artery disease (CAD),
434t
and congestive heart failure,
499t, 502t
Coronary syndromes (acute),
431-449 See also Cardiac
biomarkers,
Electrocardiogram,
Myocardial infarction,
NSTEMI, STEMI,
Unstable angina
ECG, 433
lab findings, 436
management, 437-446
TIMI risk factor score, 441t
Corticosteroid suppression, preoperative medical evaluation, 1025
1038
Cough. See also Hemoptysis,

Hiccup
differential diagnosis, 64, 65t
management, 67-69
risk assessment, 63
signs and symptoms, 65t-67t
Cough, testing, 68t
CREST syndrome, 521
Crohn disease, 643
Cryoglobulinemic vasculitis,
750t, 760-762
Cutaneous vasculitis, 750t, 762
Cystitis, 741, 746
D
Daily calorie, protein, and fat
requirements, 843t
Daily fluid requirements, 843844
Dalfopristin-quinupristin
(Synercid), 776t, 777
Death summary, 1014
Deep venous thrombosis
(DVT), 199, 205, 719
management, 209
risk and prophylaxis, 725,
726t
scoring measures, 206t
tests, 320
Defibrillator, 811
implantable, 446
Delirium
comparison to dementia, 74t
history and physical, 75
differential diagnosis, 76, 78
end of life, care, 945
management, 81, 82t
nonpharmacologic causes, 77t
pharmacologic causes, 75t-76t
physical exam, 78
reversible forms testing, 79-81
routine testing, 78-79
Dementia
causes of, 83t-84t
cognitive localization, 85t

comparison to delirium, 74t
history, 88t
management, 86
Mini-Mental State
Examination, 87t
neurologic syndromes, 86t
nonpharmacologic therapy, 89
pharmacologic therapy, 87, 89
physical exam, 81-82, 88t
Depression, comparison with
delirium and dementia, 74t
Dermatologic disorders, HIV,
561t, 597t-604t
Dextrose 5%/50%, contents,
118t
Diabetes insipidus (DI), 123
Diabetes mellitus, 529-530
emergencies, 531-537
management, 530-531
nausea and vomiting, 216t
preoperative medical evaluation, 1025-1026
Type 1 and Type 2, 529, 530t
Diabetic ketoacidosis, 421-422,
534-537
Diagnostic strategy, 985t
Dialysis
acute renal failure, 458t
definitions, 895-896
indications, 895
Diarrhea
end of life, care, 949, 951t
hyperchloremic acidosis, 424
inflammatory vs. noninflammatory, 93
Diarrhea (acute)
management, 95-96
testing, 95
Diarrhea (chronic)
management, 99-101
testing, 98-99
Diastolic dysfunction, congestive heart failure, 487,

499t, 500
Diet, and diarrhea, 93
Diet orders, 996-997
Digitalis toxicity, ECG, 367,
371i
Dilute Russell viper venom time
(DRVVT), 311
Discharge planning, 1007
Discharge summaries, 1010
coagulation (DIC), 45t,
48i, 49i, 53, 263-264, 267
Diverticula, colonic, 147-148
Diverticulitis, 9t, 10
Dix-Hallpike maneuver, 106107
Dizziness, classification, 104t
Dizziness and vertigo
differential diagnosis, 104t,
105t
management, 107-108
risk assessment, 103
testing, 105-107
DLCO (diffusing capacity of
CO), 404, 405
Do Not Resuscitate (DNR)
order, 926-928
Documentation, procedures,
875
Drug(s). See Medications
Duke activity status index, 1022
Duke criteria, infective endocarditis, 620t
Dyslipidemia
classification, 821-822
medication, 822-824
Dyspnea
causes, 112t
differential diagnosis, 110,
113t
end of life, care, 945-946,
946t, 947t
management, 110-116
oxygen therapy, 111t
1039

testing, 110, 114t
Dystonia, 274, 277t, 278
E
Echinocandins, 786-787, 788t
Elbow joint, arthrocentesis, 879
Electrical cardioversion, atrial
fibrillation, 481
Electrocardiogram (ECG), atrial
premature contraction, 330
cardiac injury, 340-351
electrolyte/medication
arrhythmias, 367
intrinsic rates, 330
normal, 327-329, 328i
P wave, 329, 349i
preexcitation syndromes, 364
PVC (premature ventricular
contraction), 330
QRS complex, 329
QRS morphology, 331-340
rate disturbances, 352-364
rhythm, 329
Electrolyte disturbances, 117130. See also Hyperkalemia, Hypernatremia,
Hypokalemia, Hyponatremia
Emergency response guidelines,
929
asystole, 937i
atrial fibrillation/flutter, 932i
atrial fibrillation/flutter with
Wolff-Parkinson-White
syndrome, 938i
bradycardia, 935i
comprehensive, 930i
PEA (pulseless electrical
activity), 936i
tachycardia, 931i
ventricular fibrillation
(VF)/pulseless ventricular
tachycardia, 934i
ventricular tachycardia, 933i
1040
Emergency response team

(ERT), 925
Empyema, 699-700
End of life, care
anorexia and weight loss, 951,
952t
constipation, 946, 949, 950t
decision making, 939-940
delirium, 945
depression and anxiety, 942945
fatigue and weakness, 952
goals, 939
insomnia, 952, 953t
pain management, 940-942
Endocarditis, preoperative prophylaxis, 1029-1031
Enteropathic arthritis, 526
Epidural abscess, back pain, 26
Epileptic seizures, 539-540
causes, 540-542, 542t
classifications, 540t
complications, 544-545
history, 543
management, 545-546, 547i
physical exam, 544
presentation, 542
status epilepticus, 548i
testing, 544
Epley maneuver, 108
Eponyms (A to Z), internal
medicine, 955-981
Equianalgesic opioid factors,
865t
Esophageal disease, HIV, 559t,
583t-584t
Esophageal spasm/reflux, 62
Esophagogastric varices, 141t,
146-147
Ethanol intoxication, 710-712
Evidence-based practice, 983988
Evidence sources, 988
Extravascular hemolysis, normocytic anemia, 17t
Exudate fluid analysis, 894t
F
Fascicular blocks, ECG, 336,
337i
Fatty diarrhea, 96, 99
Fentanyl to morphine conversion, 865t
FEV1 (forced expiratory volume
in 1 second), 403
Fever of unknown origin (FUO)
causes, 135t-137t
definitions, 131
differential diagnosis, 133t,
134t
management, 137
in subpopulations, 138t
testing, 132, 134, 137
Fibrinogen (factor I), 312t
Fluoroquinolones, 772-773, 772t
Food poisoning, diarrhea, 93
Fraction of inspired oxygen
(FIO2), 281
Framingham criteria for diagnosis of congestive heart failure, 498t
Fulminant colitis, 644t
Fulminant hepatic failure, 551553
Fungi, 791t-792t
specific treatment, 802t-804t
FVC (forced vital capacity), 403
G
Gallstone pancreatitis, 678
Gastroesophageal reflux disease
(GERD)
risk factors, 58t
symptoms, 59t
Gastrointestinal disorder
anemia, 14t
back pain, 28t, 29
HIV, 559t-560t, 577t-583t
Gastrointestinal dysfunction,
sepsis, 737-738
Gastrointestinal tract bleeding

141t, 142
history and physical, 144t
management, 146t
risk factors, 143t
testing, 142, 145, 146
usual presentation, 142t
Giant cell arteritis, 750t, 753-754
Glaucoma, 226t, 230t
Glomerulonephritis, 454, 456t
Glucose, derangements, 533t
Glucocorticoid preparations,
908t
Gout, 191t, 192, 196
Gynecologic back pain, 28t, 2930
H
HACEK group, endocarditis,
616t, 618
Head thrust (impulse) testing,
106
Headache
151t, 152, 152t-153t
management, 153, 155t-156t
testing, 153, 154t
Heart block
Mobitz I, 350, 353i
Mobitz II, 350, 354i
third degree, 350, 354i
Hematologic back pain, 28t, 30
Hematuria
causes, 161t, 162t-166t
characteristics, 161
159t-160t, 161
history, 162t-166t
lab findings, 162t-166t
management, 167-168
testing, 169i
Hemodialysis, 896-897
1041

(HUS), 259, 264
Hemophilia A (factor VIII deficiency), 52
Hemoptysis
differential diagnosis, 64, 65t,
172, 173t
history and physical, 174t175t
management, 176i-177i
massive, 63-64
risk assessment, 63, 171
testing, 172, 176i-177i
Hemorrhoids, 141t, 148
Heparin, 723-724
Heparin-induced thrombocytopenia (HIT), 259, 260,
262i, 265, 268
Hepatic failure, fulminant, 551553
Hepatitis
hepatomegaly, 186
serology, 323-325
Hepatobiliary disease, liver
function tests, 373
Hepatomegaly
causes, 181t
182
history, 182
management, 186-187
physical exam, 183-184
testing, 185i, 186
Hiccup
differential diagnosis, 69-70,
70t
signs and symptoms, 71t
High-density lipoprotein
(HDL), management, 821824
High-frequency ventilation, 836
High-output failure, congestive
heart failure, 499t, 500
History and physical, write up,
998
1042
HIV, 555-556
CD4 lymphocyte count, 557t
diagnosis and treatment, 565t604t
opportunistic infections, 605t607t
organ system involved, 558t564t
HIV-associated fever of
unknown origin, 131, 138
Homan sign, 200
Home health care orders, 10091010
Huntington disease, 278
Hypercapnia
and arterial blood gases, 285
respiratory acidosis, 427, 428
Hypercoagulable states, 720t
Hyperglycemia, and insulin,
814, 816-817
Hyperkalemia
acute renal failure, 458
129t
ECG, 367, 369i
management, 128t, 130
testing, 130
Hypernatremia
differential diagnosis, 121t122t, 123
management, 123-124
testing, 123
Hyperosmolar nonketotic
hyperglycemic coma, 537538
Hypertensive crisis, 609-610
causes, 610t
diagnosis, 610-611
management, 611-613
Hyperthyroidism, tests, 412
Hypoglycemia, 531-534
causes, 533t
and insulin, 819-820
Hypokalemia
differential diagnosis, 124, 125t

ECG, 367, 370i
and insulin, 820
management, 126-127
testing, 125
Hyponatremia
differential diagnosis, 119t-120t
management, 120
testing, 120
Hypotension, abdominal pain,
1, 3
Hypoxemia, oxygen therapy,
854-855
I
Idiopathic thrombocytopenic
purpura (ITP), 47, 48i,
265-266, 268
Infection. See also Sepsis
anemia, 14t, 17t
back pain, 26, 28t, 30
colitis, 644t
diarrhea, 93
fever of unknown origin, 135t
HACEK group, 616t
headaches, 154t
hepatomegaly, 181t, 186
HIV opportunistic, 605t-607t
lower extremity pain, 201t,
204, 206, 209-210
nausea and vomiting, 214t,
217t
pulmonary artery catheter, 401
rheumatoid arthritis, 523
seizures, 541
Infective endocarditis, 615-617
classification, 616t
complications, 618t
course, 639
diagnosis, 617-619
Duke criteria, 620t
management, 621, 635
medication, 622t-634t, 635,
639t
prophylaxis, 637-639, 639t,
640t
risk factors, 636
Inferior vena cava filters, 725
(IBD), 641-642
cancer surveillance, 652
complications, 644, 645t
Crohn disease, 643
diagnosis, 647, 648t-649t, 649
epidemiology, 643t
extraintestinal complications,
646-647
management, 649-652
ulcerative colitis, 642-643
Inflammatory diarrhea, 97, 99
Influenza, HIV, 574t
Informed consent forms, 1004
Inpatient status, 995
Insulin
diabetic ketoacidosis, 536,
817, 819
infusion protocol, 532t
therapy, 813-820
Intermittent tube feeding, 847848
Internship
admissions and orders, 9911001
advice, 989
change of service, 1006-1007
checkout, 1001-1003
consults, 1003-1004
discharges, 1007-1011
hospital deaths, 1011-1014
notes, 991
procedures, 1004-1006
rounds, 990-991
Interstitial patterns, chest X-ray,
294-295
Intoxications, acidosis, 423. See
also Overdoses,
Poisonings
Intravascular hemolysis, normocytic anemia, 17t
1043
Inverse ratio ventilation, 837

Iron deficiency anemia, 13t, 21,
23
Irritable bowel syndrome, diarrhea, 100
Ischemia, ECG, 340
Isolated right-heart failure, congestive heart failure, 500
J
Janeway lesions, 617
Joint pain
differential diagnosis, 190191, 191t-192t
fracture, 196
inflammatory, 191t, 192t
management, 196-198
noninflammatory, 191t, 192t
signs, 193t-195t
symptoms, 193t-195t
testing, 192-193, 193t-195t
K
Kaposi sarcoma, 575t, 582t, 597t
Keratitis, 225t, 230t
Knee joint, arthrocentesis, 880881
L
Lactated Ringer solution, contents, 118t
Lactic acidosis, 422-423
Lead poisoning, 13t
Life support, adults, 809-810
Linezolid, 776t, 777-778
Lipid mangement, 821-824
Liver disease, anemia, 34t
Liver failure, bleeding, 45, 54
Liver function
additional tests, 382, 383t385t
disease states, 376t
1044

abnormal, 377t-381t
indications, 375t
normal values, 374t
Low flow oxygen therapy, 111t
Low-density lipoprotein (LDL),
management, 821-824
Lower extremity pain
compartment syndrome, 210
deep venous thrombosis, 200,
205, 206t, 209
differential diagnosis, 200201, 201t-203t, 204
infectious, 201t, 204, 206,
209-210
management, 208-210
rheumatolgic, 202t, 204, 207208, 210
testing, 204-206
vascular, 200-201, 202t, 204205, 208
Lower gastrointestinal tract
bleeding, 141t, 142t, 145146
Lown-Ganong-Levine syndrome, ECG, 364
Lumbar puncture, 882-886
Lung. See also Chest X-ray
collapsed lobe X-ray, 304i,
305i
mediastinal compartments, 293
parenchyma and airways, 292
M
Macrocytic anemia, 14t
Macrolides, 774-775, 775t
Malignant hypertension, 609
Mallory-Weiss tears, 141t, 143t,
144t, 147
Mechanical ventilation, 825-828
complications, 836
modes of, 828-832, 836-837
strategies, 832, 833t-834t
weaning, 832, 835-836
Medications. See also

Antimicrobial agents
acute coronary syndromes,
437-440
acute pain, 867t-869t
agitation and behavioral disturbance, 83t
analgesic complications and
contraindications, 872t873t
antiepileptics, 545t, 549t
appetite stimulants, 952t
asthma, 471-472
atrial fibrillation, 479-481
cardiac arrest, 811
chronic pain, 870t-871t
constipation, 950t
COPD, 492t -493t
dementia, 87
depression or anxiety, 943t-944t
diarrhea, 951t
dyslipidemia, 822-824
dyspnea, 946t
Fever of unknown origin
from, 134t
hypertensive crisis, 612-613
induced cardiac arrhythmias,
367, 371i
infective endocarditis, 622t634t, 635, 639t
inflammatory bowel disease,
650-652
insomnia, 953t
and macrocytosis, 14t
myasthenia gravis, 658-659
nausea, 948t, 949t
neuroleptics, 945t
neutropenia, 662t, 663-664
pain syndromes, 941t
pulmonary thromboembolism,
723-724
rheumatoid arthritis, 525t
sepsis, 738-739
skin eruptions, 242t, 246-247
systemic lupus erythematosus,
514t
steroids, 908t
tremor, 272, 274
tube feeding, 845-846
ventricular rate control, 479t
Meningococcal meningitis, 248
Metabolic acidosis, 417, 420t
acute renal failure, 458
causes, 422t
with increased anion gap, 422i
management, 421-425
with normal anion gap, 424t
Metabolic alkalosis, 417-418,
420t, 425-426
causes, 426t
Metronidazole, 776t, 777
Microcytic anemia, 13t. 20i
Microscopic polyangiitis, 750t,
758-760
Migraine headache, 150, 152t,
155t
Mini-Mental State Examination,
87t
Mixed acid-base disorders, 418419, 421
Monoarthritis, 191t
Monobactam, 768
Multiple sclerosis, 278
Myasthenia gravis, 653-654
cholinergic crisis, 655
complications, 655
corticosteroids, 655, 905t
diagnosis, 656-657
management, 657-659
myasthenic crisis, 655
Mycobacterium avium complex
(MAC), HIV, 569t, 578t,
605t
Myocardial infarction (MI), 57,
431, 436-437
cardiac enzyme levels, 287
dyspnea, 113t, 114t, 116
ECG, 340-346, 342i, 343i
management, 447i, 448i
NSTEMI, 431, 432, 433, 437441
1045
oxygen therapy, 853

risk factors, 58t
signs, 60t
STEMI, 431, 432, 433, 441446
symptoms, 59t
Myocardial ischemia, and anemia, 11-12
Myocyte necrosis, 287, 288
Myoglobin, 288
N
Nasoenteric tube feeding, 844
Nausea and vomiting
differential diagnosis, 212213, 216t-217t
end of life, care, 948t, 949t
historical clues, 216t-217t
management, 215, 218
testing, 213, 214t, 215
Neuroimaging, 80
Neuromuscular junction disorders, 653. See also
Myasthenia gravis
Neuromuscular rigidity, 271
Neuro-otologic testing, 105-107
Neuropsychometric testing, 80
Neutropenia
causes, 662t
growth factor use, 665
management of fever, 663-664
testing, 663
Neutropenic fever of unknown
origin, 131, 138
New-onset hemolysis, 12
Noncoronary chest pain, 56
Noninvasive positive pressure
ventilation (NPPV), 837839
Nonketotic hyperosmolar syndrome, 819
1046
Nonopioid analgesics, 863t

Normal fluids, 118t
Normocytic anemia, 14t, 17t
Nosocomial fever of unknown
origin, 131, 138
Nosocomial pneumonia, 697,
700
Nosocomial sepsis, 729
NSTEMI (non-ST-segment elevation MI), 431, 432, 433,
437-441
Nutrition
oral supplementation, 842
parenteral, 842, 848-851
requirements, 843t
tube feeding, 842, 844-848
Nystagmus, 105-106
O
Ocular and visual abnormalities
management, 230t, 231t-232t
red eye, 220, 222t, 223t-226t,
230
testing, 222-223
white eye, 221, 222t, 227t229t, 231t-232t
Oliguria, abdominal pain, 3
Opioid analgesics, 863t
Oral disease, HIV, 559t, 581t582t
Organ donation, 1013
Osler nodes, 617
Osmotic diarrhea, 96, 99
Osteomalacia, 31
Outpatient status, 994, 995996
Overdoses
acetaminophen, 708-710
definition, 705
digoxin, 714-716
ethanol, 710-712
ethylene glycol, 712-713

management, 707-708
methyl alcohol, 713-714
salicylates, 716
tests, 706, 707
toxidromes, 706
tricyclic antidepressants, 717
Oxygen therapy
complications, 858-859, 859t
delivery devices, 853, 854t
indications, 853-856
limits, 859t
monitoring, 856-857
prescribing, 857-858
Oxygenation variables, 281
P
Paget disease, back pain, 31
Pain
abdominal, 1-10
acute symptom-oriented prescribing, 867t-869t
back, 25-39
chronic symptom-oriented
prescribing, 870t-871t
Pain management
classification, 863t
definitions, 861
end of life, care, 940-942
patient-controlled analgesia,
862-865
tips, 865-866
Palliative care, 939. See also
End of life, care
Palpitations
arrhythmic, 235t
differential diagnosis, 234235, 235t, 236t
management, 236-238
nonarrhythmic, 236t
testing, 236
Pancreatic insufficiency, diarrhea, 100
Pancreatitis, 9-10, 9t, 667-668

inflammatory bowel disease,
646
Pancreatitis (acute), 668t, 669t
complications, 673t
course, 678-679
diagnosis, 688, 671-675, 674t
etiology, 670t-671t
management, 675-678
severity, 680t
tests, 675t
Pancreatitis (chronic), 668t,
669t, 679
causes, 682t
classification, 679, 681
complications, 685t
course, 685
management, 683, 684-685
severity, 681t
signs and symptoms, 682
tests, 683t, 684t
PaO2/FIO2 ratio, 284
Paracentesis, 886-890
Parasitic diarrhea, 93
Parenteral nutrition, 842, 848850
complications, 851
monitoring, 850-851
Parkinson disease, 275, 279-280
Partial liquid ventilation, 836837
Patient-centered care, 983
Patient-controlled analgesia
(PCA), 862-864
dosage, 864t
Peak expiratory flow (PEF),
470-471
Penicillins, 764-766, 764i
Peptic ulcer disease (PUD)
gastrointestinal tract bleeding,
141t, 143t, 144t, 146
risk factors, 58t
symptoms, 59t
Percutaneous coronary intervention (PCI), 443, 444
1047
Percutaneous transluminal coronary angioplasty (PTCA),

1022
Pericardial diseases
constrictive, 691-692, 693694, 695
definitions, 687
effusion, 338, 340
management, 694
right and left heart catheterization, 694
signs and symptoms, 690
tamponade, 338, 340, 690691, 693, 694-695
tests, 692-694
types, 688t-689t
Pericarditis, 6
ECG, 348i
Peripheral nervous system disorders, HIV, 562t, 594t596t
Peripheral smears, anemias, 19t
Peritoneal dialysis, 898
Pharmaceuticals. See
Medications
Pharmacologic cardioversion,
atrial fibrillation, 481
Physical exam
abdominal pain, 2
anemia, 12-13
acute renal failure, 455t
bleeding disorders, 46t
congestive heart failure, 502
delirium, 78
dementia, 88t
epileptic seizures, 544
hepatomegaly, 183-184
splenomegaly, 252
thrombocytopenia, 263
wheezing, 467t
Physical findings, bleeding disorders, 46t
Plasma
coagulation disorders, 45t
derivatives transfusion, 921t
disorders, 43t-44t
1048
production, 260t, 261t

tests, 314
transfusions, 47, 51, 917t-919t
Pleural effusion, chest X-ray, 299
Pleural fluid analysis, 894t
Pneumonia
aspiration, 698, 701, 702
diagnosis, 700-701
dyspnea, 113t, 114t, 115
epidemiology, 698
HIV, 558t, 565t-577t
management, 701-703
nosocomial, 697, 700, 702
organisms causing, 697
severity, 701t
Pneumothorax, 61, 64, 466-468
chest X-ray, 295-296
dyspnea, 113t, 114t, 116
and pulmonary artery catheter,
398
Poisonings. See also
Intoxications, acidosis;
Overdoses
definition, 705
ethylene glycol, 712-713
management, 707-708
methyl alcohol, 713-714
tests, 706, 707
toxidromes, 706
Polyarteritis nodosa, 750t, 754755
Polyarthritis, 192t
Polyenes, 785-789
Polymyalgia rheumatica, 198
back pain, 28t, 33
Positive end-expiratory pressure
(PEEP), 827, 828
Positive pressure ventilators,
837
Postpyloric feeding, 844
Potassium (K), replacement, 126t
Premature ventricular contraction (PVC), 330

cardiac disease, 1018, 1019t1021t, 1022
corticosteroid suppression, 1025
diabetes mellitus, 1025-1026
endocarditis prophylaxis,
1029-1031
goals, 1015
pulmonary disease, 1023-1025
tests, 1016-1018
thromboembolism prophylaxis, 1026, 1027t-1028t,
1029
Prepyloric feeding, 844
Pressure control ventilation, 831
Pressure support ventilation,
831-832
Primary central nervous system
vasculitis, 750t, 755-756
PRN orders, at checkout, 1002
Procedures
arthrocentesis, 876-882
documentation, 875
intern guide to, 1004-1006
lumbar puncture, 882-886
paracentesis, 886-890
thoracentesis, 890-893
Proportional-assist ventilation,
837
Protein C, hypercoagulability,
315, 316t, 720t
Protein S, hypercoagulability,
316t, 319, 720t
Prothrombin (coagulation factor
II), 309i, 312t, 317t, 720t
Psoriatic arthritis, 526-527
back pain, 28t, 33
PT (prothrombin time), coagulation panel, 308, 309i,
310t, 312t, 313t
Pulmonary artery catheter, 389,
390i
complications, 398, 400-401
contraindications, 296
insertion, 392-394
limitations, 394, 396
pulmonary artery occlusion

pressure, 389, 395i, 396
placement, 401-402
troubleshooting, 396-397
use indications, 392
waveforms, 39li, 395i
Pulmonary artery occulsion
pressure (PAOP), 389,
395i, 396, 397, 399t
Pulmonary disease, preoperative
medical evaluation, 10231025
Pulmonary dysfunction, sepsis,
735-736
Pulmonary embolus (PE), 719
chest X-ray, 298
dyspnea, 115-116
risk factors, 58t
signs, 60t
symptoms, 59t
Pulmonary function tests
additional testing, 408-409
definitions, 403-404
interpretation, 406-408
Pulmonary thromboembolism,
719-720
deep venous thrombosis prophylaxis, 725, 726t
diagnosis, 721-723
management, 723-725
presentation, 720
ventilation-perfusion (V/Q)
scan, 721, 722t
Pulseless electrical activity
(PEA), 809, 811-812
Pulsus paradoxus, 499t
Pyelonephritis, 741, 746
Q
QRS morphology
bundle branch block, 331,
333, 334i, 335i
electrical axis, 331, 333, 333i
fascicular blocks, 336, 337i
1049
Ranson criteria, acute pancreatitis severity, 680t

Rash
causes, 241t
cutaneous findings, 244t-246t
descriptive terms, 240t
242t-243t
history, 242t-243t
management, 243-244, 246247
symptoms, 242t-243t
testing, 243, 244t-246t
Raynaud phenomenon, 509,
518, 520
Reactive arthritis, 526
Red blood cells (RBCs)
destruction in splenomegaly,
256
transfusion in anemia, 23
transfusion therapy, 915t-916t
Red eye, 220, 222t, 223t-226t,
230
Reiter syndrome, 526
Renal biopsy, 454-455
Renal disorder
anemia, 15t
back pain, 28t, 32
hematuria, 159t-160t
HIV, 563t
sepsis, 737
Renal failure. See Acute renal
failure
Renal replacement therapies,
895
continuous, 898-900
intermittent, 896-898
transplantation, 900
Renal tubular acidosis (RTA),
424, 425
Reptilase time (RT), 310t, 311
Respiratory acidosis, 418, 420t,
426-428
causes, 427t
1050
Respiratory alkalosis, 418, 420t,

428
causes, 429t
Reticulocyte index (RI), 19
Retinal detachment, 228t, 231t
Retinitis, HIV, 593t-594t
Rheumatoid arthritis, 521-522
complications, 523
diagnosis, 523-524
drug therapy, 525t, 907t
management, 524
presentation, 522
Rheumatologic disorder
back pain, 28t, 32
lower extremity pain, 202t,
204, 207-208, 210
Rigidity, abdominal pain, 2
Rocky Mountain Spotted Fever,
242t, 247
Romberg sign, 107
Roth spots, 617
Rumack-Matthew nomogram,
708, 709i
S
Sarcoidosis
chest X-ray, 306i
splenomegaly, 256
Scleritis, 230t, 334t
Scleroderma (limited), 521
Scleroderma (systemic), 518519
diagnosis, 520
management, 520
Seizures. See Epileptic seizures
Sepsis
cardiovascular failure, 736-737
coagulopathy, 738
definitions, 727
diagnosis, 730-732, 731t
epidemiology, 727-728
gastrointestinal dysfunction,
737-738
management, 732-739
nosocomial, 729
organ failure, 733
organisms, 728-729, 729t
pulmonary dysfunction, 735736
renal dysfunction, 737
tests, 732
Seronegative arthritis, inflammatory bowel disease, 646
Seronegative spondyloarthropathies, 524-527
Serum profiles, selected anemias, 18t
Shoulder joint, arthrocentesis,
878-879
Sickle cell disease
back pain, 28t, 30
hematuria, 164t
splenomegaly, 253
Silhouette sign, chest X-ray,
293-294
Sinoatrial (SA) node blocks,
ECG, 350, 351i
Sinopulmonary disease, HIV,
558t, 565t
Sinus arrest, ECG, 350, 351
Sjgren syndrome, 514-515
diagnosis, 516
management, 516
presentation, 515
Skin lesions, descriptive terms,
240t
Snake bites, anemia, 17t
Sodium (Na), replacement
formula, 121
Spirometry, 404-405
Splenomegaly
congestive, 250t, 256
250t, 251-252
infiltrative, 250t, 256-257
management, 254-257
physical exam, 252
RBC destruction, 250t, 256

testing, 252, 253t-254t, 254,
255t
thrombocytopenia, 261t, 269
work hypertrophy, 250t, 254255
Staphyloccocal toxic shock syndrome, 247
Status asthmaticus, 465-466
Status epilepticus, 548i
STEMI (non-ST-segment elevation MI), 431, 432, 433,
441-446
Steroid therapy
complications, 902
indications by medical specialty, 903t-907t
prescribing, 901
supraphysiologic dose side
effects, 909t-910t
Streptoccocal toxic shock syndrome, 248
Subarachnoid hemorrhage,
150t, 154t, 155t
Synchronized intermittent
mandatory ventilation
(SIMV), 830-831
Synovial fluid analysis, 883t
Systemic inflammatory
response syndrome
(SIRS), 727, 738
(SLE), 509
complications, 512
diagnosis, 510t, 512-513
drug therapy, 514t, 907t
management, 513-514
Systolic dysfunction, congestive
heart failure, 487, 499t
T
Tachyarrhythmia, 236-238
ECG, 352, 358, 359i, 360i,
361i, 362i, 363-364
1051
Tachycardia
abdominal pain, 1, 3
palpitations, 234-235
Tachypnea, abdominal pain, 1
Takayasu arteritis, 750t, 752
Tamponade pericarditis, 690691, 693, 694-695
Telithromycin, 775t
Tetanus, 271, 273
Thoracentesis, 890-893
Three-step Analgesic Ladder
(WHO), 862
Thrombin time (TT), 310t, 311,
312t
Thrombocytopenia. See also
coagulation, Hemolytic
uremic syndrome, Heparininduced thrombocytopenia,
Idiopathic thrombocytopenic purpura,
Thromobotic thrombocytopenic purpura
261, 262i
history, 263
management, 267-269
physical exam, 263
platelet production, 260t, 261t
splenomegaly, 261t, 269
testing, 266
Thromboembolic disease,
inflammatory bowel
disease, 646
Thromboembolism, preoperative prophylaxis, 1026,
1027t-1028t, 1029
Thrombotic thrombocytopenic
purpura (TTP), 48i, 51, 264
Thyroid function tests, 411-415
Thyroid-stimulating hormone
(TSH), 411, 414i
Tigecycline, 774t
1052
Torsades de pointes ECG, 358,

362i
Tourette syndrome, 280
Toxic megacolon, 644t
Transfusion therapy
coagulation factor products,
922t-924t
plasma derivatives, 921t
platelets, 917t-919t
RBCs, 915t-916t
WBCs, 917t
Transtubular potassium gradient
(TTKG), 127, 129t
Transudate fluid analysis, 894t
Trauma, and back pain, 28t, 3536
Tremor and movement disorders. See also Ataxia,
Chorea, Dystonia
descriptive terms, 274-275
differential diagnosis, 276t277t
management, 279-280
testing, 278-279
Trimethoprim-sulfamethoxazole,
775-776, 776t
Troponin, 287-288
Tuberculosis, HIV, 568t-569t,
591t-592t, 605t
Tumors, back pain, 26, 36
U
Ulcerative colitis, 642-643, 904t
Uncomplicated urinary tract
infection (UTI), 741-742
diagnosis, 744-745
Unstable angina (UA), 57, 431,
433, 437-441
and coronary artery disease,
434t
and myocardial infarction, 435t
risk factors, 58t

symptoms, 59t
management, 449i
Upper gastrointestinal tract
bleeding, 141t, 142t, 145
Uremia, 45t
Urinalysis, acute renal failure,
457t
Urinary anion gap acidosis, 423
Urinary tract infections
bacteriuria, 744t, 747
complicated, 741, 746
diagnosis, 744-745
hematuria, 162t, 167
uncomplicated, 742-745
upper/lower tract, 742t
Urosepsis, inflammatory bowel
disease, 647
Urticaria, 243-244
Uveitis, 225t, 226t, 230t
V
Validity criteria, 985
Valsalva effect, back pain, 26
Vancomycin, 771-772
Vascular disorder
back pain, 28t, 36
bleeding, 44t
lower extremity pain, 200201, 202t, 204-205, 208
Vasculitis, 749
Churg-Strauss syndrome,
750t, 756-757
complications, 751
cryoglobulinemic, 750t, 760762
cutaneous, 750t, 762
giant cell arteritis, 750t, 753754
management, 751
microscopic polyangiitis,
750t, 758-760
polyarteritis nodosa, 750t,
754-755
primary CNS, 750t, 755-756,

905t
syndrome classification, 750t
Takayasu arteritis, 750t, 752
Wegener granulomatosis,
750t, 757-758
Venous thromboembolism
(VTE), 720, 724, 725
Ventilation-perfusion (V/Q)
scan, 721, 722t
Ventricular activation time
(VAT), 328
Ventricular fibrillation
ECG, 364, 366i
Ventricular hypertrophy, ECG,
336, 338, 339i
ECG, 358, 362i, 363t, 365i
Vertigo, causes of, 105t
Vestibular neuritis, 108
Viruses, 792t-793t
specific treatment, 805t
Vitreous hemorrhage, 227t, 231t
von Willebrand disease, 48i,
50i, 51-52
W
Waddell signs, 31
Warfarin, 724-725
Warfarin-induced coagulopathy,
52
Weaning
mechanical ventilation, 832,
835-836
ventilation, 839
parameters, 835t
Wegener granulomatosis, 750t,
757-758
Wernicke encephalopathy, 272,
273
1053
Wheezing. See also Asthma

history, 466t
physical exam, 467t
Whipple disease, fever of
unknown origin from,
135t
Whipple triad, hypoglycemia,
531
White eye, 221, 222t, 227t-229t,
231t-232t
1054
Wilson disease, 277-278, 279,

280
Wolff-Parkinson-White
syndrome
ECG, 364, 368i
emergency response, 938i
Work hypertrophy,
splenomegaly, 250t, 254255
Wrist joint, arthrocentesis, 879880

Mayo Medical Manual PDF

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Mayo Medical Manual PDF

Uploaded by

Copyright:

Available Formats

Mayo Clinic

This page intentionally left blank

Guilherme H. M. Oliveira, M.D.

MAYO CLINIC SCIENTIFIC PRESS

This page intentionally left blank

Kevin A. Bybee, M.D.

Ives R. De Chazal, M.D.

Javier D. Finkielman, M.D.

Thomas M. Habermann, M.D.

Stephen M. Lange, M.D.

Professor of Neurology, Mayo Clinic College of Medicine;

Clinic; Assistant Professor of Ophthalmology, Mayo Clinic College

Professor of Medicine, Mayo Clinic College of Medicine; Rochester,

Kirby D. Slifer, D.O.

Clinic; Assistant Professor of Medicine, Mayo Clinic College of

This page intentionally left blank

Ocular and Visual Abnormalities Sanjay V. Patel, B.M.,

Asthma Augustine S. Lee, M.D.; Jason Persoff,

acquired immunodeficiency syndrome

This page intentionally left blank

I SIGNS & SYMPTOMS

IS THE PATIENTS LIFE AT RISK?

Altered Mental Status

Tachypnea and Low Oxygen Saturation

ADDRESSING THE RISK

I SIGNS & SYMPTOMS

Altered Mental Status

Table 1. Differential Diagnosis by Anatomical Location

Right upper quadrant

I SIGNS & SYMPTOMS

DIFFERENTIATING THE DIFFERENTIAL

Table 3. Differentiating by Etiology

Table 4. Differentiating by Organ System

I SIGNS & SYMPTOMS

DIAGNOSTIC TEST ORDERING

Table 5. Appropriate Tests According to Signs and

ABG, arterial blood gases; RUQ, right upper quadrant.

I SIGNS & SYMPTOMS

NPO except oral medication

*These antibiotics are suggestions and can be modified as indicated

by the clinical scenario.

Aggressive fluid therapy because fluid depletion is usually

*These antibiotics are suggestions and can be modified as indicated

by the clinical scenario.

I SIGNS & SYMPTOMS

IS THE PATIENTS LIFE AT RISK?

If hemoglobulin is <10 g/dL and/or hematocrit is 30%,

Evidence of New-Onset Hemolysis

I SIGNS & SYMPTOMS

Table 1. Microcytic AnemiaMean Corpuscular

Table 2. Macrocytic AnemiaMean Corpuscular

Table 3. Normocytic AnemiaMean Corpuscular

Table 4. Iron Deficiency Anemia

Table 5. Medications Associated With Macrocytosis

Table 6. Differential Diagnosis of Decreased Production in Normocytic Anemias

Bone marrow failure/infiltration

I SIGNS & SYMPTOMS

Collagen vascular disease

Bone marrow failure/infiltration

I SIGNS & SYMPTOMS

AIHA, autoimmune hemolytic anemia; HELLP, hemolytic anemia, elevated

Table 8. Serum Profiles of Selected Anemias

Normocytic/ Normocytic Variable Microcytic/